miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF

Author(s): Benping Zhang, Ling Ma, Jia Wei, Jingyu Hu, Zichu Zhao, Youping Wang, Yan Chen, Fei Zhao.

Journal Name: Current Cancer Drug Targets

Volume 16 , Issue 9 , 2016

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Abstract:

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.

Keywords: AKT, c-MET, dexamethasone sensitivity, miR-137, MITF, multiple myeloma, phosphorylation.

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Article Details

VOLUME: 16
ISSUE: 9
Year: 2016
Page: [807 - 817]
Pages: 11
DOI: 10.2174/1568009616666160203114140
Price: $58

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