CRNDE affects the malignant biological characteristics of human glioma stem cells by negatively regulating miR-186
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Jian Zheng1, Xiao-dong Li1, Ping Wang2,3, Xiao-bai Liu1, Yi-xue Xue2,3, Yi Hu1, Zhen Li1, Zhi-qing Li2,3, Zhen-hua Wang4, Yun-hui Liu1
1Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
2Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China
3Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China
4Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110001, China
Yun-hui Liu, e-mail: [email protected]
Keywords: long non-coding RNAs, CRNDE, microRNAs, miR-186, glioma stem cells
Received: January 28, 2015 Accepted: July 02, 2015 Published: July 13, 2015
The long non-coding RNA Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that activated early in colorectal neoplasia, but it is also up-regulated in many other solid tumors. Herein, the function and underlying mechanism of CRNDE in regulating glioma stem cells (GSCs) were investigated. We found that CRNDE expression was up-regulated while miR-186 expression was down-regulated in GSCs. Overexpression of CRNDE could promote the cellular proliferation, migration, invasion and inhibit the apoptosis in GSCs. Overexpression of miR-186 exerted functions of inhibiting the proliferation, migration and invasion of GSCs and promoting apoptosis. And CRNDE decreased the expression levels of XIAP and PAK7 by binding to miR-186 and negatively regulating it. In addition, miR-186 binded to XIAP and PAK7 3′UTR region, and decrease the expression of them, thus regulating the expression levels of downstream target proteins such as caspase 3, BAD, cyclin D1 and MARK2. The in vivo effect of CRNDE and miR-186 showed that the tumor formation rate was minimum in tumor-bearing nude mice with the knockdown of CRNDE and the overexpression of miR-186. In conclusion, CRNDE played an oncogenic role of GSCs through the negative regulation of miR-186. Both CRNDE and miR-186 could be regarded as potential targets in the glioma therapy.
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