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 miR144-3p level in glioma tissues.Next, we certified that miR-144-3p specifically bound to MET 3-untranslated region (3UTR)and inhibited its expression.miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo.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.Overexpression 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 by targeting MET and then inhibiting the downstream signaling.