1. MiR-139 Inhibits Mcl-1 Expression and Potentiates TMZ-Induced Apoptosis in Glioma.
- Author
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Li, Rui‐Yan, Chen, Ling‐Chao, Zhang, Hai‐Yan, Du, Wen‐Zhong, Feng, Yan, Wang, Han‐Bing, Wen, Jin‐Qiong, Liu, Xin, Li, Xian‐Feng, Sun, Ying, Yang, Dong‐Bo, Jiang, Tao, Li, Yong‐Li, and Jiang, Chuan‐Lu
- Subjects
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MYELOID leukemia , *MICRORNA , *TUMOR suppressor genes , *CANCER cells , *ANTINEOPLASTIC agents , *GLIOBLASTOMA multiforme treatment , *GENE expression - Abstract
Aims Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression. Methods and results Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 m RNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3′-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide ( TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection. Conclusion Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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