Prognostic roles of miR-124-3p and its target ANXA7 and their effects on cell migration and invasion in hepatocellular carcinoma.

Recent studies have indicated that ANXA7 promotes progression and metastasis of hepatocellular carcinoma (HCC). In this study we found a significant negative correlation between the levels of miR-124-3p and ANXA7 protein in HCC. Level of miR-124-3p in tumor tissues was negatively correlated, while ANXA7 protein was positively correlated, with TNM stage and tumor metastasis. Furthermore, we confirmed ANXA7 was a target gene of miR-124-3p by a dual luciferase reporter assay. In vitro, up-regulation of miR-124-3p promotes apoptosis and inhibits migration and invasion of Hca-F. Bcl-2 correlates X protein (Bax) protein level was up-regulated, while ANXA7, B-cell lymphoma-2 (Bcl-2), Matrix metalloproteinase (MMP-9) and C-X-C motif chemokine 12 (CXCL12) protein levels were suppressed relative to miR-124-3p over-expression. In vivo, up-regulation of miR-124-3p suppresses lymph node metastasis (LNM) and tumorigenicity of Hca-F cells. The expression of ANXA7, MMP-9, and CXCL12 protein in transplanted tumors was suppressed relative to miR-124-3p overexpression. In addition, we found the levels of Bcl-2, MMP-9, and CXCL12 in Hca-F cells decreased significantly after transfection of shRNA-Anxa7 in vitro. In conclusion, our study revealed miR-124-3p inhibits tumor growth, invasion, and lymphatic metastasis in HCC by down-regulation of ANXA7 gene, thereby reducing the expression of Bcl-2, MMP-9, and CXCL12.