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

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

Volume: 16 Issue: 9

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

Affiliation:

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

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.

Cite this article as:

Zhang Benping, Ma Ling, Wei Jia, Hu Jingyu, Zhao Zichu, Wang Youping, Chen Yan and Zhao Fei, miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF, Current Cancer Drug Targets 2016; 16 (9) . https://dx.doi.org/10.2174/1568009616666160203114140