Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27kip1 in vitro and in vivo.

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level. Emerging evidence suggests that altered regulation of miRNA may be involved in the pathogenesis of several types of cancers. In the current study, an inverse relationship between the expression of miR-221/miR-222 and the cell cycle inhibitor p27Kip1 was identified in U251 glioma cells. Co-suppression of miR-221/222 directly resulted in the up-regulation of p27Kip1 in the tested cells, consequently, affects their growth potential by reducing a G1 to S shift in the cell cycle. Consistently, miR-221/222 knocked-down through antisense 2'-OME-oligonucleotides increased p27Kip1 in U251 glioma subcutaneous mice and strongly reduced tumor growth in vivo through up regulation of p27Kip1. Our results suggest that miR-221/222 is a regulator of the tumor suppressor gene p27Kip1, and co-suppression of miR-221/222 expression in advanced gliomas may inhibit glioma cell proliferation by a mechanism involving the up-regulation of p27Kip1 in vitro and in vivo.