Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3′-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.

Abstract. Emerging evidence has indicated that microRNAs (miRNAs) are frequently dysregulated and are fundamental in the pathogenesis of hepatocellular carcinoma (HCC). However, the roles of miR-195 in HCC have not been well elucidated. In the present study, the expression of miR-195 was determined to be markedly downregulated in HCC tissues and cell lines, as compared with normal liver cells. Restoration of miR-195 expression resulted in significant inhibition of the proliferation and tumorigenicity of HCC cells in vitro and in vivo. Gene expression data and luciferase reporter assays revealed that miR-195 is able to directly inhibit the expression of astrocyte elevated gene 1 (AEG-1) through interaction with its 3' untranslated region. Consistently, an inverse correlation between miR-195 and AEG-1 expression was observed in HCC tissues. Furthermore, the overexpression of AEG-1 was able to partially attenuate the miR-195-induced inhibition of cell growth and promotion of apoptosis. Taken together, these findings indicate that miR-195 functions as a tumor suppressor by inhibiting AEG-1. This pathway may provide new insights into the potential molecular mechanisms of HCC.

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