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长链非编码RNA FALEC通过EZH2对ECM1进行表观遗传沉默,从而抑制舌鳞状细胞癌的增殖和转移。

Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2.

作者信息

Jia Bo, Xie Tao, Qiu Xiaoling, Sun Xiang, Chen Jun, Huang Zhijie, Zheng Xianghuai, Wang Zhiping, Zhao Jianjiang

机构信息

Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People's Republic of China.

Department of Stomatology, Shunde Hospital, Southern Medical University, Foshan 528300, People's Republic of China.

出版信息

Aging (Albany NY). 2019 Jul 23;11(14):4990-5007. doi: 10.18632/aging.102094.

Abstract

Tongue squamous cell carcinoma (TSCC), the most common epithelial cancer identified in the oral cavity, has become one of the most common malignancies across the developing countries. Increasing evidence indicates that long non-coding RNAs (lncRNAs) serve as important regulators in cancer biology. The focally amplified long non-coding RNA in epithelial cancer (FALEC) was found downregulated in the tissues of tongue squamous cell carcinoma (TSCC) and was predicted to present a good prognosis by bioinformatics analysis. Experiments indicated that FALEC knockdown significantly increased the proliferation and migration of TSCC cells both and ; however, FALEC overexpression repressed these malignant behaviors. RNA pull-down and RNA immunoprecipitation demonstrated that FALEC could recruit enhancer of zeste homolog 2 (EZH2) at the promoter regions of extracellular matrix protein 1 (ECM1), epigenetically repressing ECM1 expression. The data revealed that FALEC acted as a tumor suppressor in TSCC and may aid in developing a novel potential therapeutic strategy against TSCC.

摘要

舌鳞状细胞癌(TSCC)是口腔中最常见的上皮癌,已成为发展中国家最常见的恶性肿瘤之一。越来越多的证据表明,长链非编码RNA(lncRNAs)在癌症生物学中起重要调节作用。在上皮癌中局灶性扩增的长链非编码RNA(FALEC)在舌鳞状细胞癌(TSCC)组织中被发现下调,并且通过生物信息学分析预测其预后良好。实验表明,FALEC敲低显著增加了TSCC细胞的增殖和迁移;然而,FALEC过表达抑制了这些恶性行为。RNA下拉和RNA免疫沉淀表明,FALEC可以在细胞外基质蛋白1(ECM1)的启动子区域募集zeste同源物2增强子(EZH2),表观遗传抑制ECM1表达。数据显示,FALEC在TSCC中起肿瘤抑制作用,并可能有助于开发一种针对TSCC的新型潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd74/6682530/757d7109750b/aging-11-102094-g001.jpg

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