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// Dejun Bao 2, 3, 4, * , Chuandong Cheng 2, 3, 4, * , Xiaoqiang Lan 1, 5, * , Rong Xing 1 , Zhuo Chen 7 , Hua Zhao 8 , Junyan Sun 1 , Yang Wang 1 , Chaoshi Niu 2, 3, 4 , Bo Zhang 5 , Shengyun Fang 6 1 Department of Pathophysiology, School of Basic Medical Science, Dalian Medical University, Dalian, China 2 Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China 3 Anhui Provincial Stereotactic Neurosurgical Institute, Hefei, China 4 Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, China 5 Department of Neurosurgery, 2nd Hospital of Dalian Medical University, Dalian, China 6 Center for Biomedical Engineering and Technology, Department of Physiology, Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, Maryland, USA 7 Anhui Provincial Cancer Hospital (West Branch of Anhui Provincial Hospital), Hefei, China 8 Department of Clinical Laboratory, Cancer Hospital, Chinese Academy of Science, Hefei, China * These authors contributed equally to this work Correspondence to: Yang Wang, email: wang_yang10@aliyun.com Chaoshi Niu, email: niuchaoshi@163.com Bo Zhang, email: zhangbo@126.com Shengyun Fang, email: sfang@umaryland.edu Keywords: AR signaling, SVIP, cell proliferation, serum testosterone, p53 Received: November 22, 2016 Accepted: February 08, 2017 Published: February 19, 2017 ABSTRACT The incidence of glioma in men is higher than that in women; however, little is known about the expression and basic function of the androgen receptor (AR) in gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the transcriptional level was previously reported. The present study shows that the protein level of AR is highly expressed in cell lines of the nervous system. Moreover, the AR expression is increased while SVIP expression is decreased in tumor tissue of glioma patients, which is in agreement with the progressing WHO grades. A statistically significant increase in serum testosterone level of glioma patients compared with that of non-cancer patients was also detected. Furthermore, it has been proved that SVIP is down-regulated as well as AR is up-regulated in glioma cell lines with R1881 treatment. Interestingly, the depletion of SVIP using siRNA facilitated cell proliferation and decreased p53 expression. In addition, overexpression of SVIP increased cell death only in p53 wt cell lines. Moreover, U87MG cells, p53 wt cell line was susceptible to AR antagonists in vitro and in vivo . The current study provides insight into the biological role of AR in suppressing SVIP and p53 and promoting the progression of glioma as well as the clinical treatment of glioma patients.

// Dong-Xue Li 1, 2 , Xiao-Rui Fei 2 , Yong-Fei Dong 2 , Chuan-Dong Cheng 2 , Yang Yang 2 , Xue-Fei Deng 3 , Hai-Liang Huang 3 , Wan-Xiang Niu 2 , Chen-Xu Zhou 2 , Cheng-Yu Xia 2 and Chao-Shi Niu 2 1 Shandong University, Jinan, Shandong, China 2 Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China 3 School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China Correspondence to: Chao-Shi Niu, email: niuchaoshi@126.com Keywords: CRNDE, glioma, miR-136-5p, Bcl-2, Wnt2 Received: June 16, 2017 Accepted: September 08, 2017 Published: October 04, 2017 ABSTRACT The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.