LncRNA XIST acts as a tumor suppressor in prostate cancer through sponging miR-23a to modulate RKIP expression

Abstract

// Yang Du 1, * , Xiao-Dong Weng 1, * , Lei Wang 1, * , Xiu-Heng Liu 1 , Heng-Cheng Zhu 1 , Jia Guo 1 , Jin-Zhuo Ning 1 and Cheng-Cheng Xiao 1 1 Department of Urology, Ren’min Hospital of Wuhan University, Wuhan, Hubei 430000, China * These authors have contributed equally to this work Correspondence to: Xiu-Heng Liu, email: phoenixneo@126.com Heng-Cheng Zhu, email: zhuhcgj@aliyun.com Keywords: prostate cancer, long non-coding RNA, XIST, miR-23a, RKIP Received: June 29, 2017     Accepted: August 27, 2017     Published: October 10, 2017 ABSTRACT Accumulating evidences have indicated that aberrant expression of long non-coding RNAs (LncRNAs) is tightly associated with cancer development. Previous studies have reported that lncRNA XIST regulates tumor malignancies in several cancers. However, the underlying mechanism of XIST in prostate cancer remains unclear. In the current study, we found that XIST was down-regulated in prostate cancer specimens and cell lines. Low expression of XIST was correlated with poor prognosis and advanced tumor stage in prostate cancer patients. In gain and loss of function assays, we confirmed that XIST suppressed cellular proliferation and metastasis in prostate cancer both in vitro and in vivo . Furthermore, we found that XIST negatively regulates the expression of miR-23a and subsequently promotes RKIP expression at post-transcriptional level. Consequently, we investigated the correlation between XIST and miR-23a, and identified miR-23a as a direct target of XIST. In addition, over-expression of miR-23a efficiently abrogated the up-regulation of RKIP induced by XIST, suggesting that XIST positively regulates the expression of RKIP by competitively binding to miR-23a. Taken together, our study indicated that lncRNA XIST acts as a tumor suppressor in prostate cancer, and this regulatory effect of XIST will shed new light on epigenetic diagnostics and therapeutics in prostate cancer.