Xiong Yaoyao, Wang Long, Li Yuan, Chen Minfeng, He Wei, Qi Lin
Department of Cardiopulmonary Bypass, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
Cell Physiol Biochem. 2017;43(1):405-418. doi: 10.1159/000480419. Epub 2017 Aug 31.
BACKGROUNDS/AIMS: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR.
XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed.
XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively.
These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.
背景/目的：长链非编码RNA（lncRNA）X染色体失活特异性转录本（XIST）参与多种肿瘤的进展。据报道，lncRNA与miRNA或miRNA的靶基因之间的相互作用在恶性肿瘤中起关键作用。此外，雄激素受体（AR）被认为参与膀胱癌的进展。在本研究中，我们调查了XIST在人膀胱癌中的作用及其与miR-124和AR的相互作用。
检测膀胱肿瘤样本和细胞系中XIST和AR的表达。分析XIST和AR对膀胱癌细胞生长、侵袭和迁移的影响。采用生物信息学分析和荧光素酶测定法鉴定XIST、AR和miR-124之间的相互作用。对膀胱癌样本中miR-124与XIST和AR的相关性进行统计学分析。
XIST和AR在膀胱癌组织中上调且呈正相关。XIST和AR表达较高与膀胱癌较差的TNM分期相关。敲低XIST可降低膀胱癌细胞的增殖、侵袭和迁移。而这种抑制作用可通过AR过表达部分恢复。XIST通过直接靶向抑制miR-124表达。此外，miR-124可与AR的3'UTR结合以调节其表达。抑制miR-124可部分恢复敲低XIST诱导的AR、c-myc、p27、MMP13和MMP9表达的降低。在膀胱癌组织中，miR-124水平分别与XIST和AR的表达呈负相关。
这些发现表明，XIST可能是一种致癌lncRNA，通过miR-124依赖的AR调节促进膀胱癌的生长、侵袭和迁移。
