Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression
Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression
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DOI：
10.1016/j.bbrc.2016.08.030
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发表时间：
2016-09-16
影响因子：
3.1
通讯作者：
Gong, Cheng
中科院分区：
文献类型：
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作者：
Fang, Jing;Sun, Cheng-Cao;Gong, Cheng
最近，长链非编码RNA（IncRNA）已被确定为许多类型的癌症，包括非小细胞肺癌（NSCLC）的关键调节因子。X失活特异性转录本（XIST）在胃癌和肝细胞癌中表达上调，是一种癌基因，但其在非小细胞肺癌中的表达模式、生物学功能及机制尚不清楚。在这里，我们将XIST鉴定为通过驱动NSCLC中的肿瘤发生的致癌IncRNA。我们发现XIST在NSCLC中过度表达，其水平升高与生存期缩短和预后不良相关。XIST基因的敲除可抑制NSCLC细胞的体外增殖、迁移和侵袭能力，并抑制NSCLC细胞的体内致瘤性。RNA免疫沉淀（RIP）和RNA下拉实验表明，XIST可以同时与EZH2相互作用，抑制其潜在靶点KLF2的转录。此外，挽救实验表明，XIST的致癌功能部分取决于沉默KLF2表达。总的来说，我们的研究结果阐明了XIST过度表达如何赋予NSCLC致癌功能。(C)2016 Elsevier Inc. All rights reserved.
Recently, long noncoding RNAs (IncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic IncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis. Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically, RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that XIST could simultaneously interact with EZH2 to suppress transcription of its potential target KLF2. Additionally, rescue experiments revealed that XIST's oncogenic functions were partly depending on silencing KLF2 expression. Collectively, our findings expound how XIST over-expression endows an oncogenic function in NSCLC. (C) 2016 Elsevier Inc. All rights reserved.