MicroRNA-425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma-derived growth factor
|
|
- Natalie Merritt
- 6 years ago
- Views:
Transcription
1 ONCOLOGY LETTERS MicroRNA-425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma-derived growth factor WENYAN ZHU 1, YONGCHI MA 1, XUQIN ZHUANG 2 and XIN JIN 1 Departments of 1 Otolaryngology-Head and Neck Surgery, and 2 Pharmacy, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu , P.R. China Received January 5, 2017; Accepted November 22, 2017 DOI: /ol Abstract. Nasopharyngeal carcinoma (NPC), which arises from the nasopharynx epithelium, is most common in Southeast Asia, particularly in Southern China. To date, a variety of micrornas have been demonstrated to serve key functions in the progression and development of NPC. microrna 425 (mir 425) has previously been reported to be frequently abnormally expressed in a number of different types of human cancer, including lung, gastric, cervical, breast and prostate cancer. However, to the best of our knowledge, the expression patterns, functions and underlying mechanisms of mir 425 in NPC remain largely unexplored. In the present study, the expression of mir 425 was revealed to be low in NPC tissues and cell line. Resumption of mir 425 expression suppressed cell viability and invasion in NPC. Hepatoma derived growth factor (HDGF) was identified as a direct target gene of mir 425 in NPC. HDGF was highly expressed at mrna and protein levels in NPC tissues. Additionally, HDGF mrna was negatively correlated with mir 425 expression in NPC tissues. Furthermore, overexpression of HDGF almost completely rescued the tumor suppressing effects of mir 425 on NPC cell viability and invasion. Taken together, these results demonstrated that mir 425 acted as a tumor suppressor in NPC by targeting HDGF, suggesting that it may be a novel therapeutic target for the treatments of patients with NPC. Introduction Nasopharyngeal carcinoma (NPC), which arises from the nasopharynx epithelium, is most common in Southeast Asia, Correspondence to: Professor Wenyan Zhu, Department of Otolaryngology-Head and Neck Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu , P.R. China E mail: wenyan_zhu@126.com Key words: nasopharyngeal carcinoma, hepatoma derived growth factor, microrna 425, treatments particularly in Southern China (1). A previous study demonstrated that genetic susceptibility, environmental factors and Epstein Barr virus latent infection are key risk factors in the pathogenesis of NPC (2). Despite considerable progress having been made in multimodal treatments, the prognosis of patients with NPC remains unsatisfactory (3). The 5 year survival rate of NPC cases at I/II stage is 72 90%, however the rate markedly decreases to <55% in patients at III/IV stage (4). The key causes for poor prognosis of patients with NPC are local recurrence and metastasis (5,6). In addition, ~70% of patients being diagnosed at late stages with cervical lymph node metastasis is also a cause of treatment failure in patients with NPC (7). Therefore, elucidating the underlying molecular mechanisms of NPC initiation and progression is required, as well as the identification of novel therapeutic targets for the treatment of patients with NPC. The discovery of micrornas (mirnas) established a novel method for targeted therapy. mirnas are a large family of conserved, single stranded nucleotide long non protein coding RNA molecules (8). These small RNAs act crucial gene regulators at the posttranscriptional level by binding to the 3' untranslated region (3'-UTR) of their target genes, and thereby resulting in either modulation of translation efficiency or degradation of the target mrnas (9,10). mirnas have been demonstrated to be involved in various cellular biological processes, including proliferation, cell cycle, apoptosis, differentiation, metabolism, motility and angiogenesis (8,11,12). It has been widely established that a single mirna may be able to target hundreds of mrnas, and ~50% of mirnas are located at cancer associated chromosomal regions (13). Abnormally expressed mirnas have been observed in the majority of tumor types, including NPC (14 16). mirnas may act as either a tumor suppressor or oncogene in human cancer, depending on the functions of their target genes (17,18). Therefore, it is important to investigate the deregulated expression of mirnas and their functions in NPC in order to provide effective and novel therapeutic targets for antitumor therapy. mir 425 has previously been reported to be frequently abnormally expressed in a number of different types of human cancer (19 21). However, to the best of our knowledge, the expression pattern and biological effects of mir 425 in NPC
2 2 ZHU et al: mir-425 IN NASOPHARYNGEAL CARCINOMA have yet to be elucidated. The aim of the present study was to investigate the expression levels of mir 425 in NPC tissues and cell lines. Additionally, its functions and underlying molecular mechanisms in NPC were explored. Materials and methods Ethical statement and tissue samples. The present study was approved by the Ethical Committee of Huai'an First People's Hospital (Huai'an, China). All patients provided written consent and were informed of the purposes of the study. A total of 15 nasopharyngeal carcinoma tissues were obtained from patients (9 males, 6 females; age range, years) who underwent surgical resection at the Department of Otolaryngology Head and Neck surgery, Huai'an First People's Hospital between July 2014 and January In addition, 10 normal nasopharyngeal tissues were collected from biopsy negative cases from the same location. None of the patients received any pre operative chemotherapy or radiotherapy. All tissue samples were immediately frozen in liquid nitrogen and stored at 80 C for further study. Cell lines and culture condition. The human NPC cell line SUNE 1 and normal nasopharyngeal epithelial cell line NP69 were obtained from American Type Culture Collection (ATCC; Manassas, VA, USA). NPC cells were cultured in Dulbecco's modified Eagle's medium (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) containing 10% fetal bovine serum (FBS; Gibco; Thermo Fisher Scientific, Inc.) and 1% antibiotics (100 U/ml penicillin and 100 mg/ml streptomycin sulfates). NP69 cells were cultured in keratinocyte serum free medium (Thermo Fisher Scientific, Inc. supplemented with 30 µg/ml bovine pituitary extract (BD Biosciences, Franklin Lakes, NJ, USA). All cells were maintained in an incubator at 37 C, with 90% humidity and 5% CO 2. Oligonucleotide transfection. The mir 425 mimics and negative control mirna mimics (mir NC) were purchased from Guangzhou RiboBio Co., Ltd. (Guangzhou, China). The mir 425 mimics sequence was as follows: 5' AAU GAC ACG AUC ACU CCC GUU GA 3' and the mir NC sequence was as follows: 5' UUC UCC GAA CGU GUC ACG UTT 3'. pcdna3.1 HDGF and pcdna3.1 blank vectors were synthesized by Chinese Academy of Sciences (Changchun, China). For cell transfection, NPC cells were seeded in 6 well plates at a density of 60 70% confluence h prior to transfection. Lipofectamine 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) was used for transfection, according to manufacturer's instructions. mir 425 mimics (100 pmol) were transfected into cells in order to overexpress mir 425, whereas pcdna3.1 HDGF (4 µg) was transfected into cells to increase HDGF expression. RNA extraction and reverse transcription quantitative polymerase chain reaction (RT qpcr). Total RNA was isolated from tissue samples and cell lines using TRIzol reagent (Thermo Fisher Scientific, Inc.) and the expression of total RNA was determined using Nanodrop 2000 (Thermo Fisher Scientific, Inc.). For mir 425 expression, TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems; Thermo Fisher Scientific, Inc.) was used to synthesize cdna. The thermocycling conditions were as follows: 16 C for 30 min, 42 C for 30 min and 85 C for 5 min. Expression of mir 425 was examined using TaqMan MicroRNA PCR kit (Applied Biosystems; Thermo Fisher Scientific, Inc.), according to the manufacturer's instructions. To quantify HDGF mrna expression, reverse transcription was conducted using PrimeScript RT reagent kit and HDGF mrna was amplified using SYBR Premix Ex Taq (both from Takara Biotechnology Co., Ltd., Dalian, China), according to the manufacturer's instructions. The temperature protocol for reverse transcription was as follows: 37 C for 15 min and 85 C for 5 sec. U6 and β actin were used as internal control for mir 425 and HDGF, respectively. The PCR primers used in the present study were as follows: mir 425 forward, 5' ACA CTC CAG CTG GGA ATG ACA CGA TCA CTC C 3' and reverse, 5' TGG TGT CGT GGA GTC G 3'; U6 forward, 5' CTC GCT TCG GCA GCA CA 3' and reverse, 5' AAC GCT TCA CGA ATT TGC GT 3'; HDGF forward, 5' ATC AAC AGC CAA CAA ATA CC 3' and reverse, 5' TTC TTA TCA CCG TCA CCC T 3'; β actin forward, 5' ATT GCC GAC AGG ATG CAG AA 3' and reverse, 5' CAA GAT CAT TGC TCC TCC TGA GCG CA 3'. Fold-changes for mir 425 and HDGF mrna expression levels were calculated using the 2 ΔΔCq method (22). MTT assay. Cell viability was evaluated using an MTT assay (Sigma Aldrich; Merck KGaA, Darmstadt, Germany). Briefly, 3x10 3 cells/well were plated in a 96 well plate and then transfected with mir 425 mimics, mir NC, pcdna3.1 HDGF or pcdna3.1, as aforementioned. Following incubation for 0, 24, 48 or 72 h at 37 C and 5% CO 2 the MTT assay was performed. A total of 20 µl MTT (5 mg/ml) was added into each well and incubated at 37 C for another 4 h. The culture medium was removed and 150 µl dimethyl sulfoxide (Sigma Aldrich; Merck KGaA) was added into each well. The optical density was determined at a wavelength of 490 nm using a microplate reader (BioTek Instruments, Inc., Winooski, VT, USA). Transwell cell invasion assay. Transwell cell invasion assays were performed to evaluate the invasive capacity of NPC cells. Following 48 h of transfection, 5x10 4 cells in 100 µl FBS free culture medium were seeded into Transwell upper chamber (24 well insert; pore size, 8 µm; Corning Inc., Corning, NY, USA) coated with Matrigel (BD Biosciences). Culture medium with 20% FBS was used in the lower chamber as the attractant. Following incubation for 48 h, cells remaining on the upper surface were mechanically removed with a cotton swab. The invasive cells were fixed in 100% methanol at room temperature for 15 min and stained with 0.5% crystal violet at room temperature for 15 min. Cell numbers were obtained from five fields per membrane under a light microscope (x200 magnification; Olympus Corporation, Tokyo, Japan). Western blotting. Primary antibodies used in the present study included mouse anti human monoclonal HDGF (sc ; 1:1,000 dilution) and mouse anti human monoclonal GAPDH (sc 32233; 1:1,000 dilution) (both from Santa Cruz Biotechnology, Inc., Dallas, TX, USA). Total protein was isolated from tissues or cells using ice cold lysis buffer (Cell Signaling Technology, Inc., Danvers, MA, USA) containing protease inhibitor cocktail (Sigma Aldrich; Merck KGaA).
3 ONCOLOGY LETTERS 3 Figure 1. Expression levels of mir 425 in NPC tissues and cells. (A) Relative expression of mir 425 in 15 NPC and 10 normal nasopharyngeal tissues, as determined using reverse transcription quantitative polymerase chain reaction. * P<0.05 compared with normal nasopharyngeal tissues. (B) Relative expression of mir 425 in NPC cell line SUNE 1 and normal nasopharyngeal epithelial cell line NP69. * P<0.05 compared with NP69. NPC, nasopharyngeal carcinoma. The protein concentration was examined using a Bicinchoninic Acid Assay kit (Pierce Biotechnology Inc., Rockford, IL, USA). Equal amounts of protein (30 µg) were separated by 10% SDS PAGE, and transferred onto polyvinylidene difluoride membranes. Following blocking the membrane with Tris buffered saline containing 0.05% Tween 20 (TBST; Beyotime Institute of Biotechnology, Haimen, China) containing 5% non fat dry milk at room temperature for 1 h, the membranes were incubated overnight at 4 C with primary antibodies. Subsequently, the membranes were washed with TBST three times and probed with corresponding anti mouse horseradish peroxidase conjugated secondary antibody (1:5,000 dilution; sc 2005; Santa Cruz Biotechnology, Inc.) for 2 h at room temperature. Protein bands were visualized using ECL detection reagent (EDM Millipore, Billerica, MA, USA). GAPDH was used as a loading control, and the relative expression level was analyzed using Quantity One software (version 4.62; Bio Rad Laboratories, Inc., Hercules, CA, USA). Target prediction for mir 425 and luciferase reporter assay. The candidate target genes of mir 425 were analyzed using the mirna target prediction programs PicTar (pictar.mdc berlin. de/) and TargetScan ( 293T cells (ATCC) were seeded into 24 well plates at a density of 50 60% confluence. Subsequently, 293T cells were co transfected using Lipofectamine 2000 with mir 425 mimics or mir NC, and PGL3 HDGF 3'UTR wild type (Wt) or PGL3 HDGF 3'UTR mutant (Mut) synthesized by Shanghai GenePharma Co., Ltd. (Shanghai, China). The cells were lysed 48 h after transfection and luciferase activities were quantified using the Dual Luciferase Reporter Assay System (Promega Corporation, Madison, WI, USA) according to manufacturer's instructions. Firefly luciferase activities were normalized to Renilla luciferase activities. Statistical analysis. All data are expressed as mean ± standard deviation. All experiments were repeated at 3 times. Significant differences between groups were measured using paired Student's t tests or one way analysis of variance (ANOVA). The Student Newman Keuls post hoc test was used following ANOVA. Spearman's correlation analysis was used to explore the correlation between mir 425 and HDGF mrna in NPC tissues. All statistical analyses were Figure 2. SUNE 1 cells were transfected with mir 425 mimics or mir NC. Following transfection, the expression of mir 425 was determined using reverse transcription quantitative polymerase chain reaction. * P<0.05 compared with mir NC. mir NC, microrna negative control. performed using SPPS 17.0 software (SPSS Inc., Chicago, IL, USA). P<0.05 was considered to indicate a statistically significant difference. Results mir 425 is downregulated in NPC tissue samples and cell. To explore the expression levels of mir 425 in NPC, RT qpcr was performed in 15 nasopharyngeal carcinoma tissues and 10 normal nasopharyngeal tissues. As presented in Fig. 1A, mir 425 expression was downregulated in NPC tissues compared with that in normal nasopharyngeal tissues (P<0.05). Expression levels of mir 425 were further measured in an NPC cell line (SUNE 1) and normal nasopharyngeal epithelial cell line NP69. Compared with NP69 cells, expression levels of mir 425 were decreased in NPC cells (Fig. 1B; P<0.05). These results suggested that mir 425 may serve key functions in NPC formation and progression. Validation of transfection efficiency in NPC cells. SUNE 1 cells expressed significantly low mir 425 expression and were selected to conduct further cell function experiments. mir 425 mimics or mir NC was transfected into SUNE 1 cells. Following transfection for 48 h, RT qpcr was performed to determine transfection efficiency. As presented in Fig. 2, mir 425 was markedly upregulated in SUNE 1 cells
4 4 ZHU et al: mir-425 IN NASOPHARYNGEAL CARCINOMA Figure 3. Effects of mir 425 overexpression on SUNE 1 cell viability and invasion. (A) The viability of SUNE 1 cells transfected with mir 425 mimics or mir NC was evaluated using an MTT assay. * P<0.05 compared with mir NC. (B) Representative images and quantification of the Transwell cell invasion assay of SUNE 1 cells transfected with mir 425 mimics or mir NC (x200 magnification). * P<0.05 compared with mir NC. mir NC, microrna negative control; OD, optical density. Figure 4. HDGF is a direct target of mir 425 in NPC. (A) HDGF contained a mir nucleotide seed match at positions of the HDGF 3' UTR. (B) Upregulation of mir 425 decreased the luciferase activities of PGL3 HDGF 3'UTR Wt, however did not affect that of PGL3 HDGF 3'UTR Mut. * P<0.05 compared with mir NC. SUNE 1 cells were transfected with mir 425 mimics or mir NC. HDGF mrna and protein levels were examined by (C) reverse transcription quantitative polymerase chain reaction and (D) western blotting. * P<0.05 compared with mir NC. HDGF, hepatoma derived growth factor; NPC, nasopharyngeal carcinoma; mir NC, microrna negative control; UTR, untranslated region; Wt, wild-type; Mut, mutant. following transfection with mir 425 mimic compared with the negative control (P<0.05). Upregulation of mir 425 suppresses viability and invasion in SUNE 1 cells. To investigate the biological functions of mir 425 in NPC progression, MTT and Transwell cell invasion assays were utilized. MTT assay indicated that the viability of SUNE 1 cells transfected with mir 425 mimics was markedly suppressed compared with cells transfected with mir NC (Fig. 3A; P<0.05). In addition, data from the Transwell cell invasion assay demonstrated that restoration expression of mir 425 decreased the cell invasion capacity in SUNE 1 cells. These results suggested that mir 425 overexpression may repress NPC cell viability and invasion. HDGF is a direct target of mir 425 in NPC. To further elucidate the molecular mechanisms by which mir 425 inhibits NPC cell viability and invasion, bioinformatic analysis was performed using PicTar and Target Scan, which revealed that HDGF harbors a potential mir 425 binding site (Fig. 4A). To confirm whether mir 425 may interact with the 3' UTR of HDGF through the complementary sequence, a luciferase reporter assay was performed in 293T cells transfected with mir 425 mimics or mir NC, and along with PGL3 HDGF 3'UTR Wt or PGL3 HDGF 3'UTR Mut. As presented in Fig. 4B, ectopic expression of mir 425 decreased the luciferase activity of PGL3 HDGF 3'UTR Wt (P<0.05), however did not affect that of PGL3 HDGF 3'UTR Mut. Subsequent experiments revealed that mir 425 overexpression significantly decreased the mrna (P<0.05;
5 ONCOLOGY LETTERS 5 Figure 5. HDGF was upregulated and inversely correlated with mir 425 expression level in NPC tissues. (A) Quantification of HDGF mrna expression in 15 NPC tissues and 10 normal nasopharyngeal tissues by reverse transcription quantitative polymerase chain reaction. * P<0.05 compared with normal nasopharyngeal tissues. (B) The protein level of HDGF in NPC and normal nasopharyngeal tissues were investigated using western blotting. (C) Spearman's correlation analysis was performed to evaluate the association between HDGF mrna and mir 425 expression level in 15 NPC tissues. T, NPC tissue; N, normal nasopharyngeal tissue; HDGF, hepatoma derived growth factor; NPC, nasopharyngeal carcinoma; mir NC, microrna negative control. Fig. 4C) and protein (P<0.05; Fig. 4D) expression of HDGF in SUNE 1 cells. Collectively, these results strongly demonstrated that HDGF is the direct target of mir 425 in NPC. HDGF expression is increased and negatively correlated with mir 425 expression level in NPC tissues. HDGF expression was further investigated in 15 NPC tissues and 10 normal nasopharyngeal tissues. The results of RT qpcr and western blotting demonstrated that HDGF mrna and protein levels were increased in NPC tissues compared with that in normal nasopharyngeal tissues (Fig. 5A and B; P<0.05). Additionally, the association between HDGF mrna and mir 425 expression level in NPC tissues was evaluated using Spearman's correlation analysis. As presented in Fig. 5C, HDGF mrna expression was inversely correlated with mir 425 level in NPC tissues (r= ; P=0.0092). HDGF mediates the tumor suppressing effects of mir 425 on NPC cell viability and invasion. To explore whether the Figure 6. Enforced expression of HDGF abolished the inhibition effects of mir 425 on NPC cell viability and invasion. (A) SUNE 1 cells were transfected with pcdna3.1 HDGF or pcdna3.1. HDGF protein levels were detected using western blotting. * P<0.05 compared with pcdna3.1. (B) The viability of SUNE 1 cells transfected with mir 425 mimics, mir NC or mir 425 mimics together with pcdna3.1 HDGF was evaluated using MTT assay. * P<0.05 compared with both mir NC, and mir 425 mimics + pcdna3.1 HDGF. (C) Representative images and quantification of the Transwell cell invasion assay of SUNE 1 cells transfected with mir 425 mimics, mir NC or mir 425 mimics together with pcdna3.1 HDGF. * P<0.05 compared with both mir NC, and mir 425 mimics + pcdna3.1 HDGF. HDGF, hepatoma derived growth factor; NPC, nasopharyngeal carcinoma; mir NC, microrna negative control; OD, optical density. biological functions of mir 425 in NPC were mediated by HDGF, rescue experiments were performed. SUNE 1 cells were transfected with pcdna3.1 HDGF to increase HDGF expression levels, which was confirmed by western blotting (Fig. 6A; P<0.05). Rescue experiments revealed that enforced expression of HDGF almost completely reversed the inhibitory effects of mir 425 overexpression on viability and invasion in SUNE 1 cells (Fig. 6B and C; P<0.05). These results provided further evidence that HDGF is a direct and functional target of mir 425 in NPC. Discussion Previous studies have reported that aberrant expression of mirnas is involved in cancer occurrence and progression, including in NPC (23 25). To date, various mirnas have
6 6 ZHU et al: mir-425 IN NASOPHARYNGEAL CARCINOMA been demonstrated to serve key functions in the progression and development of NPC, functioning as oncogenes or tumor suppressors. For example, mir 17 5p targeted p21 to promote NPC cell growth in vitro and in vivo (23). mir 15a suppressed cell proliferation and induced apoptosis in NPC through regulation of CNE1 (25). In the present study, it was revealed that mir 425 expression was low in NPC tissues and cell lines. Upregulation of mir 425 repressed NPC cell viability and invasion by directly targeting HDGF. These results suggested that mir 425 may act as a tumor suppressor in NPC through inhibiting tumor growth and metastasis. Previous studies have demonstrated that mir 425 may serve critical functions in the pathogenesis of different types of human cancer. For instance, mir 425 was highly expressed in gastric cancer cell lines and mir 425 knockdown decreased cell growth and metastasis in gastric cancer (26). In cervical cancer, mir 425 was markedly overexpressed in tumor tissues and serum, with expression level of mir 425 in tumor tissues being correlated with tumor stage and lymph node metastasis. In addition, increased expression of mir 425 in serum was markedly correlated with TNM stage and lymph node metastasis (27). In esophageal squamous cell carcinoma (ESCC), mir 425 was upregulated and positively associated with cell proliferation, colony formation, migration and invasion of ESCC (20). In addition, mir 425 expression was identified to be increased in chemoresistant colorectal cancer cells and downregulation of mir 425 improved the chemosensitivity of colorectal cancer cells to 5 fluorouracil (21). However, in melanoma, mir 425 was downregulated in tumor tissues and cell lines, resumption expression of mir 425 suppressed melanoma cell growth and motility (19). These conflicting results demonstrate that expression and functions of mir 425 are tissue specific. Together these findings suggest that mir 425 may be worthy of investigation as a potential anticancer drug for certain types of cancer. It is generally accepted that mirnas exert their biological functions through negative regulation of their downstream target genes. Previous studies have validated several target genes of mir 425, including phosphatase and tensin homolog (28) in gastric cancer, insulin like growth factor 1 (19) in melanoma, mothers against decapentaplegic homolog 2 (20) in ESCC, and programmed cell death 10 (21) in colorectal cancer. In the present study, HDGF was identified as a novel direct and functional target of mir 425 in NPC. First, bioinformatic analysis indicated a mir 425 binding site in the 3' UTR of HDGF. Second, a luciferase reporter assay revealed that mir 425 may directly target the 3' UTR of HDGF. Third, upregulation of mir 425 decreased HDGF expression at mrna and protein level in NPC cells. Fourth, HDGF was upregulated in NPC tissues and inversely correlated with mir 425 expression level. Finally, restoration of HDGF almost completely abrogated the tumor suppressor function of mir 425 in NPC cells. However, a specific mirna may directly target multiple genes. Therefore, other targets of mir 425, in addition to HDGF, need to be investigated in NPC in the future. HDGF, located on chromosome 1, region q21-q23, is a heparin binding growth factor (29). It was originally purified from culture medium conditioned by HuH7 hepatoma cells (30). HDGF was highly expressed and correlated with poor prognosis in different types of human cancer, including lung (31), gastric (32), cervical (33), breast and prostate cancer (34). Furthermore, functional experiments revealed that HDGF is correlated with numerous cancer associated biological processes, including cell proliferation, anti apoptosis, angiogenesis and metastasis (35,36). In NPC, HDGF was upregulated and significantly associated with T stage and clinical stage; in addition, patients with NPC with high HDGF expression levels exhibited poorer overall survival rates compared with those with low expression of HDGF (37). Therefore, regarding cancer associated functions, HDGF may be investigated as a potential therapeutic target for the treatments of NPC. In conclusion, the present study demonstrated that mir 425 was frequently downregulated in NPC tissues and cells. Restoration expression of mir 425 attenuated NPC cell viability and invasion. Notably, HDGF was identified as a direct and functional target of mir 425 in NPC. These results suggested that mir 425/HDGF interactions may be developed as a novel strategy in the future with respect to control of the rapid growth and metastasis of NPC. References 1. Chen W: Cancer statistics: Updated cancer burden in China. Chin J Cancer Res 27: 1, Tao Q and Chan AT: Nasopharyngeal carcinoma: Molecular pathogenesis and therapeutic developments. Expert Rev Mol Med 9: 1 24, Rottey S, Madani I, Deron P and Van Belle S: Modern treatment for nasopharyngeal carcinoma: Current status and prospects. Curr Opin Oncol 23: , Jia WH, Huang QH, Liao J, Ye W, Shugart YY, Liu Q, Chen LZ, Li YH, Lin X, Wen FL, et al: Trends in incidence and mortality of nasopharyngeal carcinoma over a year period (1978/ ) in Sihui and Cangwu counties in southern China. BMC Cancer 6: 178, Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ and Ma J: How does intensity modulated radiotherapy versus conventional two dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys 80: , Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, Deng XW, Lu TX, Cui NJ and Zhao C: Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: Long term results of a phase 2 study. Cancer 117: , Chen Scarabelli C, Kaza AR and Scarabelli T: Syncope due to nasopharyngeal carcinoma. Lancet Oncol 6: , Ambros V: The functions of animal micrornas. Nature 431: , He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet 5: , Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell 136: , Ambros V: MicroRNA pathways in flies and worms: Growth, death, fat, stress, and timing. Cell 113: , Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 6: , Ma XP, Zhang T, Peng B, Yu L and Jiang de K: Association between microrna polymorphisms and cancer risk based on the findings of 66 case control studies. PLoS One 8: e79584, Liu N, Jiang N, Guo R, Jiang W, He QM, Xu YF, Li YQ, Tang LL, Mao YP, Sun Y and Ma J: mir 451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma. Mol Cancer 12: 123, Wu D, Zhou Y, Pan H, Zhou J, Fan Y and Qu P: MicroRNA 99a inhibiting cell proliferation, migration and invasion by targeting fibroblast growth factor receptor 3 in bladder cancer. Oncol Lett 7: , Wu D, Niu X, Pan H, Zhou Y, Qu P and Zhou J: MicroRNA 335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1. Mol Med Rep 13: , 2016.
7 ONCOLOGY LETTERS Fabbri M, Ivan M, Cimmino A, Negrini M and Calin GA: Regulatory mechanisms of micrornas involvement in cancer. Expert Opin Biol Ther 7: , Zhang B, Pan X, Cobb GP and Anderson TA: micrornas as oncogenes and tumor suppressors. Dev Biol 302: 1 12, Liu P, Hu Y, Ma L, Du M, Xia L and Hu Z: mir 425 inhibits melanoma metastasis through repression of PI3K Akt pathway by targeting IGF 1. Biomed Pharmacother 75: 51 57, Liu L, Zhao Z, Zhou W, Fan X, Zhan Q and Song Y: Enhanced expression of mir 425 promotes esophageal squamous cell carcinoma tumorigenesis by targeting SMAD2. J Genet Genomics 42: , Cristóbal I, Madoz Gúrpide J, Rojo F and García Foncillas J: Potential therapeutic value of mir 425 5p in metastatic colorectal cancer. J Cell Mol Med 20: , Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real time quantitative PCR and the 2( Delta Delta C(T)) method. Methods 25: , Chen C, Lu Z, Yang J, Hao W, Qin Y, Wang H, Xie C and Xie R: mir 17 5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21. Cancer Med 5: , Sun KY, Peng T, Chen Z, Huang J and Zhou XH: MicroRNA 1275 suppresses cell growth, and retards G1/S transition in human nasopharyngeal carcinoma by down regulation of HOXB5. J Cell Commun Signal 10: , Zhu K, He Y, Xia C, Yan J, Hou J, Kong D, Yang Y and Zheng G: MicroRNA 15a inhibits proliferation and induces apoptosis in CNE1 nasopharyngeal carcinoma cells. Oncol Res 24: , Zhang Z, Li Y, Fan L, Zhao Q, Tan B, Li Z and Zang A: microrna 425 5p is upregulated in human gastric cancer and contributes to invasion and metastasis in vitro and in vivo. Exp Ther Med 9: , Sun L, Jiang R, Li J, Wang B, Ma C, Lv Y and Mu N: MicoRNA 425 5p is a potential prognostic biomarker for cervical cancer. Ann Clin Biochem 54: , Liu J, Li T, Zhang N, Yang X, Wang Z, Ma J, Gu X, Fan Y and Cai D: MiR 425 up regulation induced by interleukin 1beta promotes the proliferation of gastric cancer cell AGS. Zhonghua Yi Xue Za Zhi 94: , 2014 (In Chinese). 29. Bao C, Wang J, Ma W, Wang X and Cheng Y: HDGF: A novel jack of all trades in cancer. Future Oncol 10: , Huang JS, Chao CC, Su TL, Yeh SH, Chen DS, Chen CT, Chen PJ and Jou YS: Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. Biochem Biophys Res Commun 315: , Zhang J, Qi J, Guo Y, Guo Y, Fu W, Zhou B, Wu G, Han L and He A: Aberrant expression of HDGF and its prognostic values in surgically resected non small cell lung cancer. Zhongguo Fei Ai Za Zhi 14: , Yamamoto S, Tomita Y, Hoshida Y, Takiguchi S, Fujiwara Y, Yasuda T, Doki Y, Yoshida K, Aozasa K, Nakamura H and Monden M: Expression of hepatoma derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma. Clin Cancer Res 12: , Tsai CC, Huang SC, Tai MH, Chien CC, Huang CC and Hsu YC: Hepatoma derived growth factor upregulation is correlated with prognostic factors of early stage cervical adenocarcinoma. Int J Mol Sci 15: , Guo Z, He Y, Wang S, Zhang A, Zhao P, Gao C and Cao B: Various effects of hepatoma derived growth factor on cell growth, migration and invasion of breast cancer and prostate cancer cells. Oncol Rep 26: , Li SZ, Zhao YB, Cao WD, Qu Y, Luo P, Zhen HN, Chen XY, Yan ZF and Fei Z: The expression of hepatoma derived growth factor in primary central nervous system lymphoma and its correlation with angiogenesis, proliferation and clinical outcome. Med Oncol 30: 622, Enomoto H, Nakamura H, Liu W, Iwata Y, Nishikawa H, Takata R, Yoh K, Hasegawa K, Ishii A, Takashima T, et al: Down regulation of HDGF inhibits the growth of hepatocellular carcinoma cells in vitro and in vivo. Anticancer Res 35: , Wang S and Fang W: Increased expression of hepatoma derived growth factor correlates with poor prognosis in human nasopharyngeal carcinoma. Histopathology 58: , This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
Berberine Sensitizes Human Ovarian Cancer Cells to Cisplatin Through mir-93/ PTEN/Akt Signaling Pathway
Chen Accepted: et al.: February Berberine 24, Sensitizes 2015 Ovarian Cancer Cells to Cisplatin www.karger.com/cpb 956 1421-9778/15/0363-0956$39.50/0 Original Paper This is an Open Access article licensed
More informationMicroRNA 761 is downregulated in colorectal cancer and regulates tumor progression by targeting Rab3D
EXPERIMENTAL AND THERAPEUTIC MEDICINE MicroRNA 761 is downregulated in colorectal cancer and regulates tumor progression by targeting Rab3D YUPENG REN, GANG SHI, PENG JIANG and QINGKAI MENG Department
More informationLong noncoding RNA linc-ubc1 promotes tumor invasion and metastasis by regulating EZH2 and repressing E-cadherin in esophageal squamous cell carcinoma
JBUON 2018; 23(1): 157-162 ISSN: 1107-0625, online ISSN: 2241-6293 www.jbuon.com E-mail: editorial_office@jbuon.com ORIGINAL ARTICLE Long noncoding RNA linc-ubc1 promotes tumor invasion and metastasis
More informationONCOLOGY LETTERS 15: , 2018
10098 MicroRNA 154 functions as a tumor suppressor in non small cell lung cancer through directly targeting B cell specific Moloney murine leukemia virus insertion site 1 SIDA LIU 1, YANG YANG 2, LU CHEN
More informationDownregulation of serum mir-17 and mir-106b levels in gastric cancer and benign gastric diseases
Brief Communication Downregulation of serum mir-17 and mir-106b levels in gastric cancer and benign gastric diseases Qinghai Zeng 1 *, Cuihong Jin 2 *, Wenhang Chen 2, Fang Xia 3, Qi Wang 3, Fan Fan 4,
More informationLow levels of serum mir-99a is a predictor of poor prognosis in breast cancer
Low levels of serum mir-99a is a predictor of poor prognosis in breast cancer J. Li 1, Z.J. Song 2, Y.Y. Wang 1, Y. Yin 1, Y. Liu 1 and X. Nan 1 1 Tumor Research Department, Shaanxi Provincial Tumor Hospital,
More informationMicroRNA 124 3p inhibits cell growth and metastasis in cervical cancer by targeting IGF2BP1
EXPERIMENTAL AND THERAPEUTIC MEDICINE 15: 1385-1393, 2018 MicroRNA 124 3p inhibits cell growth and metastasis in cervical cancer by targeting IGF2BP1 PING WANG 1, LI ZHANG 1, JUNHUI ZHANG 1 and GANGSHU
More informationSupplementary Table 3. 3 UTR primer sequences. Primer sequences used to amplify and clone the 3 UTR of each indicated gene are listed.
Supplemental Figure 1. DLKI-DIO3 mirna/mrna complementarity. Complementarity between the indicated DLK1-DIO3 cluster mirnas and the UTR of SOX2, SOX9, HIF1A, ZEB1, ZEB2, STAT3 and CDH1with mirsvr and PhastCons
More informationmir 491 5p inhibits osteosarcoma cell proliferation by targeting PKM2
ONCOLOGY LETTERS mir 491 5p inhibits osteosarcoma cell proliferation by targeting PKM2 TING CHEN 1, YUYANG LI 2, WENLIANG CAO 1 and YADONG LIU 3 1 Department of Orthopedics, Shengjing Hospital of China
More informationc Tuj1(-) apoptotic live 1 DIV 2 DIV 1 DIV 2 DIV Tuj1(+) Tuj1/GFP/DAPI Tuj1 DAPI GFP
Supplementary Figure 1 Establishment of the gain- and loss-of-function experiments and cell survival assays. a Relative expression of mature mir-484 30 20 10 0 **** **** NCP mir- 484P NCP mir- 484P b Relative
More informationmicrorna 761 regulates glycogen synthase kinase 3β expression and promotes the proliferation and cell cycle of human gastric cancer cells
ONCOLOGY LETTERS 16: 3459-3464, 2018 microrna 761 regulates glycogen synthase kinase 3β expression and promotes the proliferation and cell cycle of human gastric cancer cells XINFANG SUN, HONGTAO HOU,
More informationLong noncoding RNA CASC2 inhibits metastasis and epithelial to mesenchymal transition of lung adenocarcinoma via suppressing SOX4
European Review for Medical and Pharmacological Sciences 2017; 21: 4584-4590 Long noncoding RNA CASC2 inhibits metastasis and epithelial to mesenchymal transition of lung adenocarcinoma via suppressing
More informationCD31 5'-AGA GAC GGT CTT GTC GCA GT-3' 5 ' -TAC TGG GCT TCG AGA GCA GT-3'
Table S1. The primer sets used for real-time RT-PCR analysis. Gene Forward Reverse VEGF PDGFB TGF-β MCP-1 5'-GTT GCA GCA TGA ATC TGA GG-3' 5'-GGA GAC TCT TCG AGG AGC ACT T-3' 5'-GAA TCA GGC ATC GAG AGA
More informationmir-542-3p targets sphingosine-1-phosphate receptor 1 and regulates cell proliferation and invasion of breast cancer cells
European Review for Medical and Pharmacological Sciences 2017; 21: 108-114 mir-542-3p targets sphingosine-1-phosphate receptor 1 and regulates cell proliferation and invasion of breast cancer cells H.-X.
More informationmir 375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression
EXPERIMENTAL AND THERAPEUTIC MEDICINE 7: 1757-1761, 2014 mir 375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression ZHI YONG SHEN *, ZI ZHEN ZHANG *, HUA LIU, EN HAO ZHAO
More informationMir-595 is a significant indicator of poor patient prognosis in epithelial ovarian cancer
European Review for Medical and Pharmacological Sciences 2017; 21: 4278-4282 Mir-595 is a significant indicator of poor patient prognosis in epithelial ovarian cancer Q.-H. ZHOU 1, Y.-M. ZHAO 2, L.-L.
More informationCircHIPK3 is upregulated and predicts a poor prognosis in epithelial ovarian cancer
European Review for Medical and Pharmacological Sciences 2018; 22: 3713-3718 CircHIPK3 is upregulated and predicts a poor prognosis in epithelial ovarian cancer N. LIU 1, J. ZHANG 1, L.-Y. ZHANG 1, L.
More informationClinical value of combined detection of mir 1202 and mir 195 in early diagnosis of cervical cancer
ONCOLOGY LETTERS 17: 3387-3391, 2019 Clinical value of combined detection of mir 1202 and mir 195 in early diagnosis of cervical cancer XIELAN YANG 1, ZHILING YAN 1, HONGYING YANG 1, HUIJING NI 1, LEI
More informationMicroRNA 338 3p targets SOX4 and inhibits cell proliferation and invasion of renal cell carcinoma
5200 MicroRNA 338 3p targets SOX4 and inhibits cell proliferation and invasion of renal cell carcinoma ZHIGANG TONG 1, XIANFENG MENG 1, JINSONG WANG 1 and LIXIN WANG 2 1 Department of Urinary Surgery,
More informationExpression of mir-1294 is downregulated and predicts a poor prognosis in gastric cancer
European Review for Medical and Pharmacological Sciences 2018; 22: 5525-5530 Expression of mir-1294 is downregulated and predicts a poor prognosis in gastric cancer Y.-X. SHI, B.-L. YE, B.-R. HU, X.-J.
More informationKnockdown of Long Noncoding RNA LUCAT1 Inhibits Cell Viability and Invasion by Regulating mir-375 in Glioma
Oncology Research, Vol. 26, pp. 307 313 0965-0407/18 $90.00 +.00 Printed in the USA. All rights reserved. DOI: https://doi.org/10.3727/096504017x15088061795756 Copyright Ó 2018 Cognizant, LLC. E-ISSN 1555-3906
More informationMicroRNA 19a promotes nasopharyngeal carcinoma by targeting transforming growth factor β receptor 2
EXPERIMENTAL AND THERAPEUTIC MEDICINE 14: 1419-1426, 2017 MicroRNA 19a promotes nasopharyngeal carcinoma by targeting transforming growth factor β receptor 2 FANG MA 1, ZHIYUAN WANG 2, JINGJING WANG 1,
More informationEffects of AFP gene silencing on Survivin mrna expression inhibition in HepG2 cells
mrna expression inhibition in HepG2 cells Z.L. Fang 1, N. Fang 2, X.N. Han 3, G. Huang 2, X.J. Fu 2, G.S. Xie 2, N.R. Wang 2 and J.P. Xiong 1 1 Department of Medical Oncology, The First Affiliated Hospital
More informationKnockdown of lncrna TP73 AS1 inhibits gastric cancer cell proliferation and invasion via the WNT/β catenin signaling pathway
3248 Knockdown of lncrna TP73 AS1 inhibits gastric cancer cell proliferation and invasion via the WNT/β catenin signaling pathway YUFENG WANG, SHUAI XIAO, BINGYI WANG, YANG LI and QUANNING CHEN Department
More informationPUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells
PUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells C.-G. Sun 1 *, J. Zhuang 1 *, W.-J. Teng 1, Z. Wang 2 and S.-S. Du 3 1 Department of Oncology,
More informationFigure S1. Analysis of genomic and cdna sequences of the targeted regions in WT-KI and
Figure S1. Analysis of genomic and sequences of the targeted regions in and indicated mutant KI cells, with WT and corresponding mutant sequences underlined. (A) cells; (B) K21E-KI cells; (C) D33A-KI cells;
More informationLong non coding RNA XIST serves an oncogenic role in osteosarcoma by sponging mir 137
730 Long non coding RNA XIST serves an oncogenic role in osteosarcoma by sponging mir 137 HUI LI 1*, JINGJING CUI 2*, BIN XU 3, SHUGUANG HE 4, HAIYAN YANG 5 and LINGZHI LIU 4 1 Department of Microbiology
More informationLncRNA LET function as a tumor suppressor in breast cancer development
European Review for Medical and Pharmacological Sciences 2018; 22: 6002-6007 LncRNA LET function as a tumor suppressor in breast cancer development C.-X. ZHOU, X. WANG, N. YANG, S.-K. XUE, W.-C. LI, P.-P.
More informationSupplementary Materials
Supplementary Materials 1 Supplementary Table 1. List of primers used for quantitative PCR analysis. Gene name Gene symbol Accession IDs Sequence range Product Primer sequences size (bp) β-actin Actb gi
More informationmir 205 targets runt related transcription factor 2 to inhibit human pancreatic cancer progression
ONCOLOGY LETTERS mir 205 targets runt related transcription factor 2 to inhibit human pancreatic cancer progression LU ZHUANG 1,2, JIA GUO 2, YAO YAO 1,2 and ZHAOSHEN LI 1 1 Department of Gastroenterology,
More informationCircMTO1 inhibits cell proliferation and invasion by regulating Wnt/β-catenin signaling pathway in colorectal cancer
European Review for Medical and Pharmacological Sciences 2018; 22: 8203-8209 CircMTO1 inhibits cell proliferation and invasion by regulating Wnt/β-catenin signaling pathway in colorectal cancer Z. GE,
More informationMicroRNA 98 suppresses cell growth and invasion of retinoblastoma via targeting the IGF1R/k Ras/Raf/MEK/ERK signaling pathway
INTERNATIONAL JOURNAL OF ONCOLOGY 54: 807-820, 2019 MicroRNA 98 suppresses cell growth and invasion of retinoblastoma via targeting the IGF1R/k Ras/Raf/MEK/ERK signaling pathway LONG GUO 1, YU BAI 2, SHUZHE
More informationExpression and functions of microrna-139 in osteosarcoma.
Biomedical Research 2017; 28 (22): 9879-9884 ISSN 0970-938X www.biomedres.info Expression and functions of microrna-139 in osteosarcoma. Qi Liao *, Jianghua Ming, Geliang Hu, Yaming Li, Chun Zhang, Yanchao
More informationmir-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN
mir-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN J.W. Ling 1, P.R. Lu 2, Y.B. Zhang 1, S. Jiang 1 and Z.C. Zhang 1 1 Department of Ophthalmology, Third Hospital of Zhangjiagang,
More informationSmall hairpin RNA-mediated Krüppel-like factor 8 gene knockdown inhibits invasion of nasopharyngeal carcinoma
ONCOLOGY LETTERS 9: 2515-2519, 2015 Small hairpin RNA-mediated Krüppel-like factor 8 gene knockdown inhibits invasion of nasopharyngeal carcinoma JING WANG 1, JIAN LI HU 1, RU BO CAO 1, QIAN DING 1, GANG
More informationAbbreviations: P- paraffin-embedded section; C, cryosection; Bio-SA, biotin-streptavidin-conjugated fluorescein amplification.
Supplementary Table 1. Sequence of primers for real time PCR. Gene Forward primer Reverse primer S25 5 -GTG GTC CAC ACT ACT CTC TGA GTT TC-3 5 - GAC TTT CCG GCA TCC TTC TTC-3 Mafa cds 5 -CTT CAG CAA GGA
More informationLong noncoding RNA DARS-AS1 acts as an oncogene by targeting mir-532-3p in ovarian cancer
European Review for Medical and Pharmacological Sciences 2019; 23: 2353-2359 Long noncoding RNA DARS-AS1 acts as an oncogene by targeting mir-532-3p in ovarian cancer K. HUANG, W.-S. FAN, X.-Y. FU, Y.-L.
More informationMicroRNA-132 inhibits migration, invasion and epithelial-mesenchymal transition by regulating TGFβ1/Smad2 in human non-small cell lung cancer
European Review for Medical and Pharmacological Sciences MicroRNA-132 inhibits migration, invasion and epithelial-mesenchymal transition by regulating TGFβ1/Smad2 in human non-small cell lung cancer J.-X.
More informationPlasmids Western blot analysis and immunostaining Flow Cytometry Cell surface biotinylation RNA isolation and cdna synthesis
Plasmids psuper-retro-s100a10 shrna1 was constructed by cloning the dsdna oligo 5 -GAT CCC CGT GGG CTT CCA GAG CTT CTT TCA AGA GAA GAA GCT CTG GAA GCC CAC TTT TTA-3 and 5 -AGC TTA AAA AGT GGG CTT CCA GAG
More informationMir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma
European Review for Medical and Pharmacological Sciences 2017; 21: 5624-5629 Mir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma Z. WANG 1, Y.-J.
More informationEXPERIMENTAL AND THERAPEUTIC MEDICINE 17: , 2019
EXPERIMENTAL AND THERAPEUTIC MEDICINE 17: 919-926, 2019 MicroRNA 432 is downregulated in osteosarcoma and inhibits cell proliferation and invasion by directly targeting metastasis associated in colon cancer
More informationMicroRNA 216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B
3156 MicroRNA 216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B LEI LI and HUI QIANG MA Department of Stomatology, Jining
More informationmir-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2
ONCOLOGY LETTERS mir-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2 LI YU 1, JUAN LU 1, BAO ZHANG 2, XIONG LIU 1, LU WANG 1, SI-YANG LI 1, XIAO-HONG PENG 1, XIA XU 1, WEN-DONG
More informationmicrorna 200a functions as a tumor suppressor by targeting FOXA1 in glioma
EXPERIMENTAL AND THERAPEUTIC MEDICINE microrna 200a functions as a tumor suppressor by targeting FOXA1 in glioma XIAOFENG CHEN 1, KUN LIU 1, PING YANG 2, WEIPING KUANG 1, HONGXING HUANG 1, EWEN TU 3, BO
More informationExpression of mir-146a-5p in patients with intracranial aneurysms and its association with prognosis
European Review for Medical and Pharmacological Sciences 2018; 22: 726-730 Expression of mir-146a-5p in patients with intracranial aneurysms and its association with prognosis H.-L. ZHANG 1, L. LI 2, C.-J.
More informationBHP 2-7 and Nthy-ori 3-1 cells were grown in RPMI1640 medium (Hyclone) supplemented with 10% fetal bovine serum (Gibco), 2mM L-glutamine, and 100 U/mL
1 2 3 4 Materials and Methods Cell culture BHP 2-7 and Nthy-ori 3-1 cells were grown in RPMI1640 medium (Hyclone) 5 supplemented with 10% fetal bovine serum (Gibco), 2mM L-glutamine, and 100 U/mL 6 penicillin-streptomycin.
More informationRNA extraction, RT-PCR and real-time PCR. Total RNA were extracted using
Supplementary Information Materials and Methods RNA extraction, RT-PCR and real-time PCR. Total RNA were extracted using Trizol reagent (Invitrogen,Carlsbad, CA) according to the manufacturer's instructions.
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Sherman SI, Wirth LJ, Droz J-P, et al. Motesanib diphosphate
More informationLncRNA RGMB-AS1 is activated by E2F1 and promotes cell proliferation and invasion in papillary thyroid carcinoma
European Review for Medical and Pharmacological Sciences 2018; 22: 1979-1986 LncRNA RGMB-AS1 is activated by E2F1 and promotes cell proliferation and invasion in papillary thyroid carcinoma Z. ZHANG 1,
More informationAssociation between downexpression of mir-1301 and poor prognosis in patients with glioma
European Review for Medical and Pharmacological Sciences 2017; 21: 4298-4303 Association between downexpression of mir-1301 and poor prognosis in patients with glioma Q.-L. BAI, C.-W. HU, X.-R. WANG, G.-F.
More informationmir-132 inhibits lung cancer cell migration and invasion by targeting SOX4
Original Article inhibits lung cancer cell migration and invasion by targeting SOX4 Yang Li, Lingling Zu, Yuli Wang, Min Wang, Peirui Chen, Qinghua Zhou Tianjin Key Laboratory of Lung Cancer Metastasis
More informationMicroRNA 661 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation
ONCOLOGY LETTERS MicroRNA 661 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation FEIFEI LV 1,2, KEHONG ZHENG 1, JINLONG YU 1 and ZONGHAI HUANG 1 1 Department
More informationExpression of long non-coding RNA linc-itgb1 in breast cancer and its influence on prognosis and survival
European Review for Medical and Pharmacological Sciences 2017; 21: 3397-3401 Expression of long non-coding RNA linc-itgb1 in breast cancer and its influence on prognosis and survival W.-X. LI 1, R.-L.
More informationDecreased expression of mir-490-3p in osteosarcoma and its clinical significance
European Review for Medical and Pharmacological Sciences Decreased expression of mir-490-3p in osteosarcoma and its clinical significance B. TANG, C. LIU, Q.-M. ZHANG, M. NI Department of Orthopedics,
More informationMicroRNA-98 suppresses cell proliferation, migration and invasion by targeting collagen triple helix repeat containing 1 in hepatocellular carcinoma
MOLECULAR MEDICINE REPORTS 13: 2639-2644, 2016 MicroRNA-98 suppresses cell proliferation, migration and invasion by targeting collagen triple helix repeat containing 1 in hepatocellular carcinoma CHEN
More informationmir 140 5p inhibits cell proliferation and invasion in colorectal carcinoma by targeting SOX4
ONCOLOGY LETTERS mir 140 5p inhibits cell proliferation and invasion in colorectal carcinoma by targeting SOX4 ZHONGSONG ZHAO, WEIWEI LIU and JIANHUA LI Digestive System Department, Shandong Provincial
More informationSupplemental Data. Shin et al. Plant Cell. (2012) /tpc YFP N
MYC YFP N PIF5 YFP C N-TIC TIC Supplemental Data. Shin et al. Plant Cell. ()..5/tpc..95 Supplemental Figure. TIC interacts with MYC in the nucleus. Bimolecular fluorescence complementation assay using
More informationOriginal Article mir-338-3p inhibits the proliferation and migration of gastric cancer cells by targeting ADAM17
Int J Clin Exp Pathol 2015;8(9):10922-10928 www.ijcep.com /ISSN:1936-2625/IJCEP0011715 Original Article mir-338-3p inhibits the proliferation and migration of gastric cancer cells by targeting ADAM17 Jiang-Tao
More informationEffects of VEGF/VEGFR/K-ras signaling pathways on mirna21 levels in hepatocellular carcinoma tissues in rats
Effects of VEGF/VEGFR/K-ras signaling pathways on mirna21 levels in hepatocellular carcinoma tissues in rats J.Z. Gao 1,2 *, Y.L. Wang 1 *, J. Li 2 and L.X. Wei 2 1 Medical College, Xinxiang Medical University,
More informationNature Structural & Molecular Biology: doi: /nsmb Supplementary Figure 1
Supplementary Figure 1 U1 inhibition causes a shift of RNA-seq reads from exons to introns. (a) Evidence for the high purity of 4-shU-labeled RNAs used for RNA-seq. HeLa cells transfected with control
More informationExpression level of microrna-195 in the serum of patients with gastric cancer and its relationship with the clinicopathological staging of the cancer
European Review for Medical and Pharmacological Sciences 2016; 20: 1283-1287 Expression level of microrna-195 in the serum of patients with gastric cancer and its relationship with the clinicopathological
More informationOverexpression of long-noncoding RNA ZFAS1 decreases survival in human NSCLC patients
European Review for Medical and Pharmacological Sciences 2016; 20: 5126-5131 Overexpression of long-noncoding RNA ZFAS1 decreases survival in human NSCLC patients F.-M. TIAN 1, F.-Q. MENG 2, X.-B. WANG
More informationHEK293FT cells were transiently transfected with reporters, N3-ICD construct and
Supplementary Information Luciferase reporter assay HEK293FT cells were transiently transfected with reporters, N3-ICD construct and increased amounts of wild type or kinase inactive EGFR. Transfections
More informationONCOLOGY LETTERS. XUYA ZHAO, SHI ZHOU, DAZHI WANG, WEI HE, JUNXIANG LI and SHUAI ZHANG. Received November 6, 2015; Accepted May 11, 2017
ONCOLOGY LETTERS MicroRNA 205 is downregulated in hepatocellular carcinoma and inhibits cell growth and metastasis via directly targeting vascular endothelial growth factor A XUYA ZHAO, SHI ZHOU, DAZHI
More informationmir-125a-5p expression is associated with the age of breast cancer patients
mir-125a-5p expression is associated with the age of breast cancer patients H. He 1 *, F. Xu 2 *, W. Huang 1, S.Y. Luo 1, Y.T. Lin 1, G.H. Zhang 1, Q. Du 1 and R.H. Duan 1 1 The State Key Laboratory of
More informationSupplementary Document
Supplementary Document 1. Supplementary Table legends 2. Supplementary Figure legends 3. Supplementary Tables 4. Supplementary Figures 5. Supplementary References 1. Supplementary Table legends Suppl.
More informationSupplementary Figure 1. HOPX is hypermethylated in NPC. (a) Methylation levels of HOPX in Normal (n = 24) and NPC (n = 24) tissues from the
Supplementary Figure 1. HOPX is hypermethylated in NPC. (a) Methylation levels of HOPX in Normal (n = 24) and NPC (n = 24) tissues from the genome-wide methylation microarray data. Mean ± s.d.; Student
More informationOriginal Article Tissue expression level of lncrna UCA1 is a prognostic biomarker for colorectal cancer
Int J Clin Exp Pathol 2016;9(4):4241-4246 www.ijcep.com /ISSN:1936-2625/IJCEP0012296 Original Article Tissue expression level of lncrna UCA1 is a prognostic biomarker for colorectal cancer Hong Jiang,
More informationOriginal Article microrna-195-cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma
Int J Clin Exp Pathol 2014;7(10):6871-6879 www.ijcep.com /ISSN:1936-2625/IJCEP0001737 Original Article microrna-195-cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma Niuniu Sun
More informationSupplementary Figures
Supplementary Figures Supplementary Figure 1. H3F3B expression in lung cancer. a. Comparison of H3F3B expression in relapsed and non-relapsed lung cancer patients. b. Prognosis of two groups of lung cancer
More informationReduced mirna-218 expression in pancreatic cancer patients as a predictor of poor prognosis
Reduced mirna-218 expression in pancreatic cancer patients as a predictor of poor prognosis B.-S. Li, H. Liu and W.-L. Yang Department of Gastrointestinal and Pancreatic Surgery, The Third Xiangya Hospital
More informationOriginal Article MiR-130a regulates the proliferation and metastasis of HCC cells through targeting ZEB1/2
Int J Clin Exp Pathol 2017;10(3):2744-2753 www.ijcep.com /ISSN:1936-2625/IJCEP0046135 Original Article MiR-130a regulates the proliferation and metastasis of HCC cells through targeting ZEB1/2 Ting Wang
More informationOriginal Article microrna-377 inhibits non-small-cell lung cancer through targeting AEG-1
Int J Clin Exp Pathol 2015;8(11):13853-13863 www.ijcep.com /ISSN:1936-2625/IJCEP0010479 Original Article microrna-377 inhibits non-small-cell lung cancer through targeting AEG-1 Fanlu Meng, Linlin Zhang,
More informationMicroRNA 101 inhibits cell migration and invasion in bladder cancer via targeting FZD4
EXPERIMENTAL AND THERAPEUTIC MEDICINE MicroRNA 101 inhibits cell migration and invasion in bladder cancer via targeting FZD4 LEI CHEN, YONGQI LONG, ZHIJUN HAN, ZHIZHOU YUAN, WENJIN LIU, FAN YANG, TAO LI,
More informationmir 544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang 1
ONCOLOGY LETTERS mir 544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang 1 FENG WANG 1, ZHIQIANG LI 1 and BO SUN 2 1 Department of Gastrointestinal, Thyroid and Breast
More informationa) Primary cultures derived from the pancreas of an 11-week-old Pdx1-Cre; K-MADM-p53
1 2 3 4 5 6 7 8 9 10 Supplementary Figure 1. Induction of p53 LOH by MADM. a) Primary cultures derived from the pancreas of an 11-week-old Pdx1-Cre; K-MADM-p53 mouse revealed increased p53 KO/KO (green,
More informationUpregulation of circrna_ serves as a prognostic biomarker for nasopharyngeal carcinoma and is involved in radiosensitivity
ONCOLOGY LETTERS 16: 6495-6501, 2018 Upregulation of circrna_0000285 serves as a prognostic biomarker for nasopharyngeal carcinoma and is involved in radiosensitivity MINGXIA SHUAI, JANGWEI HONG, DONGHAI
More informationINTERNATIONAL JOURNAL OF ONCOLOGY 54: , 2019
326 Paclitaxel resistant gastric cancer MGC 803 cells promote epithelial to mesenchymal transition and chemoresistance in paclitaxel sensitive cells via exosomal delivery of mir 155 5p MEI WANG 1,2, RONG
More informationProfiles of gene expression & diagnosis/prognosis of cancer. MCs in Advanced Genetics Ainoa Planas Riverola
Profiles of gene expression & diagnosis/prognosis of cancer MCs in Advanced Genetics Ainoa Planas Riverola Gene expression profiles Gene expression profiling Used in molecular biology, it measures the
More informationOriginal Article Increased LincRNA ROR is association with poor prognosis for esophageal squamous cell carcinoma patients
Int J Clin Exp Pathol 2017;10(4):4654-4660 www.ijcep.com /ISSN:1936-2625/IJCEP0048142 Original Article Increased LincRNA ROR is association with poor prognosis for esophageal squamous cell carcinoma patients
More informationEffect of lncrna LET on proliferation and invasion of osteosarcoma cells
European Review for Medical and Pharmacological Sciences 2018; 22: 1609-1614 Effect of lncrna LET on proliferation and invasion of osteosarcoma cells G. KONG 1, X.-J. QI 2, J.-F. WANG 3 1 Department of
More informationSupplementary Figure 1
Supplementary Figure 1 Supplementary Figure 1: Cryopreservation alters CD62L expression by CD4 T cells. Freshly isolated (left) or cryopreserved PBMCs (right) were stained with the mix of antibodies described
More informationLong non coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating mir 32 5p/PTEN axis
https://doi.org/10.1186/s13578-017-0192-0 Cell & Bioscience RESEARCH Open Access Long non coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating mir 32 5p/PTEN axis Zhi Qiang Gao *,
More informationLong non coding RNA NEAT1 promotes migration and invasion of oral squamous cell carcinoma cells by sponging microrna 365
EXPERIMENTAL AND THERAPEUTIC MEDICINE 16: 2243-2250, 2018 Long non coding RNA NEAT1 promotes migration and invasion of oral squamous cell carcinoma cells by sponging microrna 365 XIAOHUA LIU, WENZHI SHANG
More informationGenome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54
CORRECTION NOTICE Nat. Genet. 42, 759 763 (2010); published online 22 August 2010; corrected online 27 August 2014 Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects
More informationExpression of lncrna TCONS_ in hepatocellular carcinoma and its influence on prognosis and survival
European Review for Medical and Pharmacological Sciences 2017; 21: 5655-5660 Expression of lncrna TCONS_00027978 in hepatocellular carcinoma and its influence on prognosis and survival Q. CHEN 1, G.-D.
More informationDown-regulation of long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer
European Review for Medical and Pharmacological Sciences 2016; 20: 5143-5147 Down-regulation of long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer
More informationResearch on the inhibitory effect of metformin on human oral squamous cell carcinoma SCC-4 and CAL-27 cells and the relevant molecular mechanism.
Biomedical Research 2017; 28 (14): 6350-6354 ISSN 0970-938X www.biomedres.info Research on the inhibitory effect of metformin on human oral squamous cell carcinoma SCC-4 and CAL-27 cells and the relevant
More informationmir-187 inhibits the growth of cervical cancer cells by targeting FGF9
ONCOLOGY REPORTS 38: 1977-1984, 2017 mir-187 inhibits the growth of cervical cancer cells by targeting FGF9 Hua Liang, Ruoyu Luo, Xiaoqi Chen, Yuzi Zhao and Aili Tan Department of Obstetrics and Gynecology,
More informationTargeting effect of microrna on CD133 and its impact analysis on proliferation and invasion of glioma cells
Targeting effect of microrna on CD133 and its impact analysis on proliferation and invasion of glioma cells C. Zhao 1,2 *, Z.G. Ma 3 *, S.L. Mou 4, Y.X. Yang 2, Y.H. Zhang 2 and W.C. Yao 1 1 Department
More informationAdvances in Computer Science Research, volume 59 7th International Conference on Education, Management, Computer and Medicine (EMCM 2016)
7th International Conference on Education, Management, Computer and Medicine (EMCM 2016) Expression of Beta-Adrenergic Receptor in Glioma LN229 Cells and Its Effect on Cell Proliferation Ping Wang1, Qingluan
More informationMicroRNA-18b promotes cell proliferation and invasion in non-small cell lung cancer by directly targeting runt-related transcription factor 3.
Biomedical Research 2018; 29 (1): 71-77 ISSN 0970-938X www.biomedres.info MicroRNA-18b promotes cell proliferation and invasion in non-small cell lung cancer by directly targeting runt-related transcription
More informationPlasma Bmil mrna as a potential prognostic biomarker for distant metastasis in colorectal cancer patients
Title Plasma Bmil mrna as a potential prognostic biomarker for distant metastasis in colorectal cancer patients Author(s) Pun, JC; Chan, JY; Chun, BK; Ng, KW; Tsui, SY; Wan, TMH; Lo, OSH; Poon, TCJ; Ng,
More informationThe lncrna MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating mirna-487a
Kong et al. Cellular & Molecular Biology Letters (2019) 24:26 https://doi.org/10.1186/s11658-019-0148-y Cellular & Molecular Biology Letters RESEARCH LETTER Open Access The lncrna MIR4435-2HG is upregulated
More informationmir-218 tissue expression level is associated with aggressive progression of gastric cancer
mir-218 tissue expression level is associated with aggressive progression of gastric cancer X.X. Wang 1, S.J. Ge 2, X.L. Wang 2, L.X. Jiang 1, M.F. Sheng 2 and J.J. Ma 2 1 Department of General Surgery,
More informationSupplementary Figure 1
Supplementary Figure 1 3 3 3 1 1 Bregma -1.6mm 3 : Bregma Ref) Http://www.mbl.org/atlas165/atlas165_start.html Bregma -.18mm Supplementary Figure 1 Schematic representation of the utilized brain slice
More informationOriginal Article Reduced serum mir-138 is associated with poor prognosis of head and neck squamous cell carcinoma
Int J Clin Exp Pathol 2017;10(10):10276-10281 www.ijcep.com /ISSN:1936-2625/IJCEP0059849 Original Article Reduced serum mir-138 is associated with poor prognosis of head and neck squamous cell carcinoma
More informationmir 483-5p promotes prostate cancer cell proliferation and invasion by targeting RBM5
ORIGINAL ARTICLE Vol. 43 (6): 1060-1067, November - December, 2017 doi: 10.1590/S1677-5538.IBJU.2016.0595 mir 483-5p promotes prostate cancer cell proliferation and invasion by targeting RBM5 Zhi-Gang
More informationOriginal Article High serum mir-203 predicts the poor prognosis in patients with pancreatic cancer
Int J Clin Exp Pathol 2017;10(4):4688-4693 www.ijcep.com /ISSN:1936-2625/IJCEP0047128 Original Article High serum mir-203 predicts the poor prognosis in patients with pancreatic cancer Jun Ma, Xiaokun
More informationSupplementary Figure 1 MicroRNA expression in human synovial fibroblasts from different locations. MicroRNA, which were identified by RNAseq as most
Supplementary Figure 1 MicroRNA expression in human synovial fibroblasts from different locations. MicroRNA, which were identified by RNAseq as most differentially expressed between human synovial fibroblasts
More information