title: miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Tianjin Hospital, Tianjin, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Lan
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Man
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, PLA Airforce General Hospital, Beijing, China.
authors.forename: Tingyi
authors.initials: T
authors.lastname: Xia
authors.affiliation: Tianjin Huanhu Hospital, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; D011838:Radiation-Sensitizing Agents; D003606:Dacarbazine; D019859:Proto-Oncogene Proteins c-met; D051059:PTEN Phosphohydrolase; D000077204:Temozolomide
keywords: c-Met; glioblastoma; irradiation; miR-144-3p; temozolomide