MicroRNA-188 suppresses G ₁/S transition by targeting multiple cyclin/CDK complexes

Abstract

Background

Accelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control.

Results

Overexpression of miR-188 inhibits cell proliferation, tumor colony formation and G ₁/S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G ₁/S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation.

Conclusions

This study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G ₁/S related cyclin/CDKs and Rb/E2F signaling pathway.

Electronic supplementary material

The online version of this article (doi:10.1186/s12964-014-0066-6) contains supplementary material, which is available to authorized users.