Affiliations: [a] Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China | [b] Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China | [c] Department of Intensive Care Unit, First Hospital of Jilin University, Changchun, Jilin, China
Correspondence:
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Corresponding author: Ming Xiu, Department of Intensive Care Unit, First Hospital of Jilin University, No.71, Xinmin Street, Changchun 130021, Jilin, China. Tel.: +86 0431 188782639; Fax: +86 431 85612345; E-mail: xmxmjz1@yeah.net.
Abstract: OBJECTIVES: MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a acts as tumor suppressor in hepatocellular carcinoma (HCC) progression. However, the underlying functions for miR-29a in HCC still to be investigated. METHODS: The expression of miR-29a expression in HCC tissues and corresponding adjacent normal tissues was detected using qRT-PCR analyses. Cell proliferation ability was assessed using CCK8 assay, cell colony forming and flow cytometry analysis. Bioinformatics, the dual luciferase reporter assay, qRT-PCR and western blot analysis were used to demonstrate that SIRT1 was a target of miR-29a. RESULTS: Here, we demonstrated that miR-29a was significantly downregulated in HCC tissues compared with corresponding adjacent normal tissues. Lower miR-29a expression associated with tumor size and vascular invasion of HCC. Furthermore, Lower miR-29a predicted a poor disease free survival (DFS) and overall survival (OS) time for HCC patients. Function assays showed that overexpression of miR-29a effectively suppressed cell proliferation, cell colony forming ability, and cell cycle progression. MiR-29a overexpression also inhibited the cell cycle related protein expression of CyclinD1 and CDK4, but increasing the P21 expression. Furthermore, Bioinformatics and the dual luciferase reporter assay analysis results demonstrated that miR-29a specifically targeted the 3’-UTR of SIRT1 mRNA and regulated its protein expression. Increased SIRT1 expression rescued the inhibited effects induced by miR-29a overexpression in HCC cells. CONCLUSIONS: Thus, these results indicated that miR-29a may serve as a potential target of HCC treatment.
