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长链非编码RNA UCA1通过表观遗传抑制p21和E-钙黏蛋白的表达促进胆囊癌进展。

Long non-coding RNA UCA1 promotes gallbladder cancer progression by epigenetically repressing p21 and E-cadherin expression.

作者信息

Cai Qiang, Jin Longyang, Wang Shouhua, Zhou Di, Wang Jiandong, Tang Zhaohui, Quan Zhiwei

机构信息

Department of General Surgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200092, China.

出版信息

Oncotarget. 2017 Jul 18;8(29):47957-47968. doi: 10.18632/oncotarget.18204.

Abstract

A growing number of studies indicated that long non-coding RNAs (lncRNAs) determine some cellular processes in cancer, such as proliferation, metastasis and differentiation. Urothelial carcinoma associated 1 (UCA1), an lncRNA, had been reported for its overexpression and oncogenic effect on various human cancers. In this study, we found that UCA1 was significantly overexpressed in gallbladder cancer (GBC) and positively correlated with tumor size, lymph node metastasis, TNM stage and short survival time. Moreover, UCA1 promoted GBC cell proliferation and metastasis in vitro and tumor growth in vivo. Mechanically, we identified that UCA1 promoted GBC progression through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p21 and E-cadherin, and epigenetically suppressing their transcript.

摘要

越来越多的研究表明,长链非编码RNA(lncRNA)决定了癌症中的一些细胞过程,如增殖、转移和分化。尿路上皮癌相关1(UCA1)是一种lncRNA,已报道其在多种人类癌症中过表达并具有致癌作用。在本研究中,我们发现UCA1在胆囊癌(GBC)中显著过表达,且与肿瘤大小、淋巴结转移、TNM分期及短生存时间呈正相关。此外,UCA1在体外促进GBC细胞增殖和转移,在体内促进肿瘤生长。机制上,我们发现UCA1通过招募zeste同源物2增强子(EZH2)至p21和E-钙黏蛋白的启动子,并在表观遗传上抑制它们的转录,从而促进GBC进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7fd/5564618/f94a2da9f61e/oncotarget-08-47957-g001.jpg

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