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长链非编码RNA UCA1通过调控miR-143/HMGB1通路促进膀胱癌细胞的侵袭和上皮-间质转化。

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway.

作者信息

Luo Junhua, Chen Jing, Li Hang, Yang Yu, Yun Haichao, Yang Shangqi, Mao Xiangming

机构信息

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China.

The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China.

出版信息

Oncol Lett. 2017 Nov;14(5):5556-5562. doi: 10.3892/ol.2017.6886. Epub 2017 Sep 4.

Abstract

The long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) is an oncogenic lncRNA in bladder cancer, and its upregulation is associated with enhanced cell invasion. However, the underlying mechanism remains to be elucidated. The present study demonstrated that UCA1 was positively associated with cell invasion ability and promoted epithelial-mesenchymal transition (EMT) of bladder cancer cells by inducing high mobility group box 1 (HMGB1). Furthermore, bioinformatics and luciferase reporter assays demonstrated binding sites of the tumor suppressive miR-143 within UCA1 and the 3'untranslated region of HMGB1. UCA1 negatively regulated miR-143 expression in a dose-dependent manner in bladder cancer cells. In addition, UCA1 and HMGB1 were upregulated and miR-143 was downregulated in bladder cancer specimens. Overall, the data suggested that UCA1 may promote the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway, which exhibits an important regulatory role in the pathology of bladder cancer.

摘要

长链非编码RNA(lncRNA)尿路上皮癌相关因子1(UCA1)是膀胱癌中的一种致癌lncRNA,其上调与细胞侵袭增强有关。然而,其潜在机制仍有待阐明。本研究表明,UCA1与细胞侵袭能力呈正相关,并通过诱导高迁移率族蛋白B1(HMGB1)促进膀胱癌细胞的上皮-间质转化(EMT)。此外,生物信息学和荧光素酶报告基因检测证实了UCA1内以及HMGB1的3'非翻译区内存在肿瘤抑制性miR-143的结合位点。UCA1在膀胱癌细胞中以剂量依赖性方式负调控miR-143的表达。此外,在膀胱癌标本中UCA1和HMGB1上调,而miR-143下调。总体而言,数据表明UCA1可能通过调节miR-143/HMGB1途径促进膀胱癌细胞的侵袭和EMT,这在膀胱癌的病理过程中发挥重要的调节作用。

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