Hepatitis B Virus Affected Serum MicroRNA-203a Level in Hepatocellular Carcinoma.

BACKGROUND: MicroRNAs have been shown to play a critical role in early diagnosis of hepatocellular carcinoma. Nevertheless, microRNAs' functions in serum of patients with hepatocellular carcinoma (HCC) are not fully understood. METHODS: qRT-PCR was used to detect the expression level of microRNA-203a (miR-203a) in clinical serum samples of HCC and HepG2 cells. Kaplan-Meier method was used to estimate overall survival, and the cell scratch test was used to observe the migration ability of cells in vitro. RESULTS: Here, we first observed that serum miR-203a was significantly upregulated in HCC patients with HBV compared to without HBV. In HCC patients, miR-203a low expression was positively related with poor overall survival. In addition, we found that HBV improved the poor prognosis of HCC patients with lower miR-203a levels. After successfully constructing HepG2 cell line carrying HBV, further studies demonstrated miR-203a expression level was increased in HepG2 with HBV compared to without HBV. CONCLUSIONS: Lower serum miR-203a level in HCC patients led to worse overall survival, which depended on HBV. In vitro, miR-203a level was positively correlated with HBV. Therefore, our studies provided the novel insight into the role of serum miR-203a in HCC patients with HBV and potential new molecular target for early diagnosis of hepatitis B virus-related hepatocellular carcinoma.

RIP6 Suppresses Tumor Cell Growth in Hepatocellular Carcinoma.

BACKGROUND: Receptor-interacting protein (RIP) has been shown to play a critical role in the development of cancer cells. Nevertheless, its functional role in hepatocellular carcinoma (HCC) progression is not fully understood. METHODS: Western blotting and qRT-PCR were used to detect the expression level of RIP6 in clinical tissues of HCC and HCC cell lines; MTT methods, cells flow cytometry, plate cloning, and nude mice tumor formation were used to verify the effect of RIP6 on HCC progression in in vivo and in vitro experiments. RESULTS: Here, we first observed that RIP6 was significantly down-regulated in HCC tissue compared to adjacent normal tissues. In HCC patients, RIP6 low expression was positively related with tumor size. In addition, we found that RIP6 promoted HCC cell apoptosis to inhibit cancer progress. Further studies demonstrated RIP6 also suppressed HCC cell proliferation to further regulate cancer growth. Mechanistically, we demonstrated that RIP6 over-expression could lead to smaller tumor size in vivo. CONCLUSIONS: RIP6 inhibited tumor cell growth by promoting cell apoptosis and suppressing cell proliferation of HCC in vivo and in vitro. Therefore, our studies provided the novel insight into the role of RIP6 in HCC progress and a potential new molecular target for treating HCC.

miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7.

Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.

Diagnostic and prognostic value of miR-106a in colorectal cancer.

We sought to systematically evaluate the diagnostic and prognostic value miR106a in patients with colorectal cancer (CRC). An original study was conducted to explore correlations between tissue miR106a levels and outcomes for 138 patients diagnosed with CRC. To explore the diagnostic performance of miR106a, eligible studies were identified from medical databases from China and abroad. Based on these results, 15 studies (including our original study) were pooled and included in a meta-analyses. The pooled sensitivity, specificity, and diagnostic odds ratios of miR106a were 0.53 (95% confidence interval (CI): 0.49-0.57), 0.85 (95% CI: 0.82-0.88), and 7.22 (95% CI: 3.17-16.44) for diagnosis of CRC, and the area under the curve (AUC) for miR106a when diagnosing CRC was 0.72. Patients with higher expression of tissue miR106a had poor overall survival (pooled hazard ratio (HR): 1.50; 95% CI: 1.02-2.20), but not disease-free survival (pooled HR: 1.03; 95% CI: 0.40-2.65). Overexpression of miR106a may predict superior metastasis-free survival (pooled HR: 0.65; 95% CI: 0.33-1.27), but the effect was not significant in this study (p = 0.21).

Prognostic and clinicopathological significance of long noncoding RNA H19 overexpression in human solid tumors: evidence from a meta-analysis.

BACKGROUND: Many studies have reported that the expression level of lncRNA H19 was increased in various tumors. LncRNA H19 may play a significant role in cancer occurrence and development. An increased level of H19 was also associated with poor clinical outcomes of cancer patients. RESULTS: 12 eligible studies were screened, with a total of 1437 cancer patients. From the results of meta-analysis, as for prognosis, the patients with high expression of lncRNA H19 were shorter in OS (HR=1.08, 95% CI: 1.05-1.12). Statistical significance was also showed in subgroup meta-analysis stratified by the cancer type, analysis type and sample size. In addition, the patients detected with high H19 expression may be poorer in DFS (HR=1.27; 95% CI = 0.97-1.56). As for clinicopathology, it showed that increased H19 was related to poor histological grades (OR=2.31, 95% CI: 1.12-4.75), positive lymph node metastasis (OR=2.29, 95 % CI: 1.21-4.34) and advanced clinical stage (OR=4.83, 95% CI: 3.16-7.39). MATERIALS AND METHODS: Eligible studies were collected by retrieving keywords in PubMed, Web of Science, Embase, CNKI and Wanfang database, from 1966 to April 23, 2016. This quantitative meta-analysis was performed with Stata SE12.0 and RevMan5.3 software. It aimed to explore the association between H19 expression level and prognosis and clinicopathology. CONCLUSIONS: LncRNA-H19 may be a novel molecular marker for predicting solid tumors. It can also be a predictive factor of clinicopathological features in various cancers. Further studies are needed to verify the clinical utility of H19 in human cancers.

Association of the HOTAIR rs4759314 polymorphism with cancer risk: a meta-analysis.

PURPOSE: To explore the association between HOTAIR rs4759314 and cancer risk. METHODS: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis. RESULTS: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population. CONCLUSION: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population.

Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.