MiR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules of 21-24 nt that regulate the expression of other genes by transcriptional inhibition or translational repression. Multiple lines of evidence suggest that miRNAs play important roles in tumor development and progression. We identified 24 miRNAs markedly and aberrantly expressed in human cervical cancer. The most significantly deregulated was miR-143 as determined by miRNA microarray analysis. miR-143 was introduced into HeLa cells and it was found that the overexpression of miR-143 significantly inhibited HeLa cell proliferation and promoted apoptosis; anti-miR-143 rescued the effects. HeLa cells transfected with pre-miR-143, pre-anti-miR-143 or control miRNA precursor were injected subcutaneously into the flanks of female athymic nude mice, and the overexpression of miR-143 suppressed the formation of tumors. Compared with normal cervical tissues, the levels of Bcl-2 were increased in miR-143-downregulated tissues. Sustained overexpression of miR-143 in HeLa cells resulted in suppression of Bcl-2 expression, and knockdown of miR-143 by anti-miR-143 increased Bcl-2 expression. In addition, overexpression of Bcl-2 partially reversed the inhibition of proliferation and promotion of apoptosis in the HeLa cells caused by miR-143. Furthermore, miR-143 suppressed the activity of a luciferase reporter carrying the 3′-UTR of Bcl-2, which was abolished by mutation of the predicted miR-143-binding site, indicating that Bcl-2 is a miR-143 target gene. Our study revealed a molecular link between miR-143 and Bcl-2. Direct involvement in the regulation of Bcl-2 may be one of the mechanisms through which miR-143 may play a role in the pathogenesis of cervical cancer.