ABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Animals , Apoptosis , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Mice , Mice, NudeABSTRACT
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.
Subject(s)
Adenocarcinoma/genetics , Autophagy-Related Protein 7/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Animals , Apoptosis/genetics , Autophagy-Related Protein 7/metabolism , Base Sequence , Cell Line , Cell Line, Tumor , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , HCT116 Cells , HT29 Cells , Humans , Lymphatic Metastasis , Male , Mice , Mice, Nude , MicroRNAs/metabolism , Middle Aged , Neoplasm Staging , Neoplasm Transplantation , Prognosis , Survival AnalysisABSTRACT
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).
