Inhibition of c-FLIP expression by miR-512-3p contributes to taxol-induced apoptosis in hepatocellular carcinoma cells.

Dysregulation of the antiapoptotic protein cellular FLICE-like inhibitory protein (c-FLIP) has been proven to be associated with tumorigenesis and progress of most human cancers. However, its aberrant expression is poorly elucidated. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in tumorigenesis through negatively regulating gene expression. Our study disclosed that c-FLIP was overexpressed in HepG2 hepatocellular carcinoma cells and down-regulation of c-FLIP enhanced taxol-induced apoptosis. Taxol induction significantly decreased the protein level of c-FLIP. While no decrease in c-FLIP mRNA level was observed, indicating taxol decreased c-FLIP expression through a post-transcriptional mechanism. miR-512-3p was a predicted suppressor of c-FLIP and exhibited an opposite expression manner to c-FLIP before and after taxol induction. Luciferase report assay demonstrated miR-512-3p negatively regulated c-FLIP expression via a conserved miRNA-binding site in 3' untranslated region (3'UTR) of c-FLIP. The decrease of c-FLIP protein due to transfection of miR-512-3p further validated the inhibitory effect of miR-512-3p on c-FLIP. Additional transfection of miR-512-3p remarkably promoted taxol-induced apoptosis, confirming its involvement in apoptosis. In summary, our study disclosed a novel regulatory mechanism that down-regulation of c-FLIP by miR-512-3p contributed to taxol-induced apoptosis. Importantly, the pivotal role of miR-512-3p in determining c-FLIP abundance helps to broaden the implications for cancer therapy by developing small molecules to directly target c-FLIP at mRNA level.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}