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长链非编码RNA XIST通过靶向miR-133a促进膀胱癌细胞增殖和迁移。

Long non-coding RNA XIST promotes cell proliferation and migration through targeting miR-133a in bladder cancer.

作者信息

Zhou Keqin, Yang Jinrui, Li Xurui, Chen Wenjie

机构信息

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.

出版信息

Exp Ther Med. 2019 Nov;18(5):3475-3483. doi: 10.3892/etm.2019.7960. Epub 2019 Aug 29.

Abstract

The long non-coding RNA (lncRNA) X inactive specific transcript (XIST) has recently been reported to promote the malignant progression of bladder cancer through regulating several microRNAs (miRs), including miR-124, miR-139-5p and miR-200c. However, whether other miRs are also involved in this process has remained to be determined. The present study demonstrated that XIST was significantly upregulated in bladder cancer tissues compared with that in adjacent normal tissues. Furthermore, its expression was reduced in several common bladder cancer cell lines. High expression of XIST was significantly associated with tumour progression and poor prognosis of patients with bladder cancer. An experiment indicated that knockdown of XIST significantly reduced the proliferation and migration of bladder cancer cells. A luciferase assay suggested that XIST binds to its predicted binding site in miR-133a. In addition, it was identified that miR-133a was significantly downregulated in bladder cancer, and its expression levels were inversely correlated with those of XIST in bladder cancer tissues. Furthermore, loss- and gain-of-function experiments indicated that miR-133a acted as a downstream effector in XIST-mediated bladder cancer cell proliferation and migration. In conclusion, the present study demonstrates that XIST promotes bladder cancer cell proliferation and migration via targeting miR-133a and thus suggests that XIST may be used as a potential therapeutic target for bladder cancer.

摘要

长链非编码RNA(lncRNA)X染色体失活特异性转录本(XIST)最近被报道可通过调控几种微小RNA(miR)促进膀胱癌的恶性进展,这些miR包括miR-124、miR-139-5p和miR-200c。然而,其他miR是否也参与这一过程仍有待确定。本研究表明,与相邻正常组织相比,XIST在膀胱癌组织中显著上调。此外,它在几种常见的膀胱癌细胞系中的表达降低。XIST的高表达与膀胱癌患者的肿瘤进展和不良预后显著相关。一项实验表明,敲低XIST可显著降低膀胱癌细胞的增殖和迁移。荧光素酶报告基因检测表明,XIST与其在miR-133a中的预测结合位点结合。此外,研究发现miR-133a在膀胱癌中显著下调,其表达水平与膀胱癌组织中XIST的表达水平呈负相关。此外,功能缺失和功能获得实验表明,miR-133a在XIST介导的膀胱癌细胞增殖和迁移中起下游效应分子的作用。总之,本研究表明XIST通过靶向miR-133a促进膀胱癌细胞的增殖和迁移,因此提示XIST可能作为膀胱癌潜在的治疗靶点。

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