title: Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression.
abstract: Recently, long noncoding RNAs (lncRNAs) 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 lncRNA 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.
authors: Department of Oncology, Wuhan Pu-Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430034, PR China.
authors: Jing
authors: J
authors: Fang
authors: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, PR China. Electronic address: chengcaosun@whu.edu.cn.
authors: Cheng-Cao
authors: CC
authors: Sun
authors: Department of General Surgery, ZhongNan Hospital of Wuhan University, Wuhan 430071, PR China. Electronic address: gongcheng306@163.com.
authors: Cheng
authors: C
authors: Gong
mesh_terms: D000368:Aged; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: KLF2; Long noncoding RNA XIST; Non-small cell lung cancer (NSCLC); Proliferation; Tumorigenesis