miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 30 untranslated region of the protein tyrosine phosphatase l (PTP mu). Previous studies indicated that PTPl suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 overexpression induced a downregulation of PTPl as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPl gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPl in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPl protein expression. Oncogene (2012) 31, 858-868; doi: 10.1038/onc.2011.280;published online 11 July 2011