miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met

The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3-untranslated region (3 UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing METinvitro and invivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy bytargeting MET and then inhibiting the downstream signaling.China National Natural Scientific Fund [81201973, 81172596, 81482814]; Natural Scientific Fund of Shan Dong province [ZR2014HM011]SCI(E)PubMedARTICLEyuexiaolfm@163.com2274-28613