MicroRNA let-7g and let-7i inhibit hepatoma cell growth concurrently via downregulation of the anti-apoptoticprotein B-cell lymphoma-extra large

Abstract

Let-7 family members have been identified as tumor-suppressing microRNAs, which are important in human hepatocellular carcinoma (HCC). These family members may function differently as a result of different base sequences at the 3'end. The aim of this study was to determine the antitumor effects of miR-let-7g/i (let-7g/i) on HCC cells and to investigate whether let-7g and let-7i have a combinatorial effect on HCC. The expression levels of let-7g/i in hepatoma cells were determined by quantitative reverse transcription polymerase chain reaction. In addition, a 5-ethynyl-2'-deoxyuridine retention assay and flow cytometry analysis were used to detect the effect of let-7g/i on the proliferation and apoptosis of BEL-7402 cells, respectively. The expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-xL) was analyzed using western blot analysis. The results revealed that the expression levels of let-7g/i were significantly decreased in HCC cell lines when compared with L-02 cells. Furthermore, the overexpression of let-7g/i significantly suppressed DNA replication, inhibited cell proliferation and promoted apoptosis of BEL-7402 hepatoma cells. The expression of the anti-apoptotic protein, Bcl-xL, was inhibited by the combined role of let-7g and let-7i. We hypothesize that let-7g and let-7i exhibit a concurrent effect to regulate cell proliferation and the apoptosis of hepatoma cells, and this function is mediated by the Bcl-xL protein.