长链非编码 RNA XIST 通过调节 miR-124-3p/EZH2 增加喉鳞状细胞癌的侵袭性。
Long noncoding RNA XIST increases the aggressiveness of laryngeal squamous cell carcinoma by regulating miR-124-3p/EZH2.
机构信息
Department of Otolaryngology, The First Hospital, Jilin University, Changchun City, Jilin Province, 130021, PR China.
Department of Otolaryngology, The First Hospital, Jilin University, Changchun City, Jilin Province, 130021, PR China.
出版信息
Exp Cell Res. 2019 Aug 15;381(2):172-178. doi: 10.1016/j.yexcr.2019.04.034. Epub 2019 May 6.
The long non-coding RNAs (lncRNAs) are an emerging class of cancer regulators. The objective of the study was to elucidate the roles and underlying mechanisms of XIST in laryngeal squamous cell carcinoma. Quantitative real-time PCR (qRT-PCR) suggested that XIST was highly upregulated in laryngeal squamous cancerous (LSCC) tissues. Knockdown of XIST, mediated by lentiviral transfection of XIST-specific short-hairpin RNA (shRNA), led to the inhibition of proliferation, migration, and invasion of LSCC cells in vitro. In vivo, XIST knockdown also suppressed the growth of LSCC xenografts in mice. Upregulation of miR-124 and downregulation of EZH2 were concomitantly observed after XIST knockdown, and our data suggested that XIST served as the competitive endogenous RNA of miR-124 to modulate EZH2 expression. Moreover, ectopic overexpression of EZH2 prominently attenuated the anti-proliferation activity by XIST knockdown. Therefore, XIST plays an important role in progression of LSCC by modulating the miR-124-EZH2 axis.
长链非编码 RNA（lncRNAs）是一类新兴的癌症调控因子。本研究旨在阐明 XIST 在喉鳞状细胞癌中的作用及其潜在机制。实时定量 PCR（qRT-PCR）结果表明，XIST 在喉鳞状癌（LSCC）组织中呈高表达。通过慢病毒转染 XIST 特异性短发夹 RNA（shRNA）下调 XIST 的表达，可抑制 LSCC 细胞的体外增殖、迁移和侵袭。体内实验中，下调 XIST 表达也可抑制 LSCC 异种移植瘤在小鼠体内的生长。下调 XIST 后同时观察到 miR-124 的上调和 EZH2 的下调，我们的数据表明 XIST 作为 miR-124 的竞争性内源性 RNA 来调节 EZH2 的表达。此外，EZH2 的异位过表达显著减弱了 XIST 下调的抗增殖活性。因此，XIST 通过调节 miR-124-EZH2 轴在 LSCC 的进展中发挥重要作用。
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