Background: Multiple myeloma (MM), a clonal B cell malignancy characterized by the proliferation of plasma cells within the bone marrow, is still an incurable disease, and therefore, finding new therapeutic targets is urgently required. Although microRNA-137 (miR-137), which is involved in a variety of cellular processes, has been reported to be under-expressed in many types of solid tumors, its role in MM is less known. Methods: In this study, the target gene and the potential effect of miR-137 in MM were investigated. Results: The results showed significantly down regulated expression of miR-137 in MM cell lines and in the CD138+ bone marrow mononuclear cells of MM patients. A dual luciferase reporter gene analysis revealed that MITF is a direct target of miR-137. The overexpression of miR-137 or transfection of MITF-shRNA had no significant effect on the expression of serine/threonine protein kinase (AKT), but the expression of MITF, c-MET, p-AKT, and its phosphorylated substrate protein decreased significantly, which was accompanied by an increase in p53 expression. In addition, the overexpression of miR-137 or MITF-shRNA significantly improved the 36-hour inhibition rate and apoptosis rate in multiple myeloma cells treated with dexamethasone. The overexpression of MITF could counteract the biological effect of miR-137 in multiple myeloma cells. Conclusion: We conclude that MITF is a direct target of miR-137. The miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AKT phosphorylation via targeting MITF.
基金：
National Science Foundation of China [81101789, 81300390, 81372541]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Hematol, Wuhan 430022, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Zhang Benping,Ma Ling,Wei Jia,et al.miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF[J].CURRENT CANCER DRUG TARGETS.2016,16(9):807-817.doi:10.2174/1568009616666160203114140.
APA：
Zhang, Benping,Ma, Ling,Wei, Jia,Hu, Jingyu,Zhao, Zichu...&Zhao, Fei.(2016).miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF.CURRENT CANCER DRUG TARGETS,16,(9)
MLA：
Zhang, Benping,et al."miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF".CURRENT CANCER DRUG TARGETS 16..9(2016):807-817
