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 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. 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 by targeting MET and then inhibiting the downstream signaling. We propose that the microRNA miR‐144‐3p plays an essential anti‐tumor role in glioblastoma. A newly identified miR‐144‐3p/MET signaling axis could represent a novel target for cellular resistance to cancer therapeutic drugs and radiation in glioblastoma patients. Jak, janus kinase; Grb2, Growth factor receptor‐bound protein 2; HGF; miR, microRNA; PI3K, phosphoinositol‐3‐kinase; Raf, rapidly accelerated fibrosarcoma; STAT, Signal Transducers and Activators of Transcription. We propose that the microRNA miR‐144‐3p plays an essential anti‐tumor role in glioblastoma. A newly identified miR‐144‐3p/MET signaling axis could represent a novel target for cellular resistance to cancer therapeutic drugs and radiation in glioblastoma patients. Jak, janus kinase; Grb2, Growth factor receptor‐bound protein 2; HGF; miR, microRNA; PI3K, phosphoinositol‐3‐kinase; Raf, rapidly accelerated fibrosarcoma; STAT, Signal Transducers and Activators of Transcription.