title: miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF.
abstract: 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.
  
  
  
  In this study, the target gene and the potential effect of miR-137 in MM were investigated. .
  
  
  
  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.
  
  
  
  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.
authors: Benping
authors: B
authors: Zhang
authors: Ling
authors: L
authors: Ma
authors: Jia
authors: J
authors: Wei
authors: Jingyu
authors: J
authors: Hu
authors: Zichu
authors: Z
authors: Zhao
authors: Youping
authors: Y
authors: Wang
authors: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yanchen981@163.com.
authors: Yan
authors: Y
authors: Chen
authors: . gracezhao911@126.com.
authors: Fei
authors: F
authors: Zhao
mesh_terms: D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: C545567:MIRN137 microRNA, human; C497234:MITF protein, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering; D003907:Dexamethasone; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt