miR-137抑制AKT的磷酸化和通过靶向因子在多发性骨髓瘤细胞提高地塞米松的灵敏度

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, Fei Zhao

Affiliation:

关键词: AKT，c-Met，地塞米松敏感，miR-137，MITF，多发性骨髓瘤，磷酸化

摘要: 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:

Benping Zhang, Ling Ma, Jia Wei, Jingyu Hu, Zichu Zhao, Youping Wang, Yan Chen, Fei Zhao , 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