Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression

• Published in: Biochemical and biophysical research communications Vol. 478; no. 2; pp. 811 - 817
• Main Authors: Fang, Jing, Sun, Cheng-Cao, Gong, Cheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.09.2016
• Subjects: 60 APPLIED LIFE SCIENCES; Aged; Apoptosis; BIOLOGICAL FUNCTIONS; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement; CELL PROLIFERATION; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Humans; IN VIVO; KLF2; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Long noncoding RNA XIST; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; LUNGS; Male; Middle Aged; Neoplasm Staging; Non-small cell lung cancer (NSCLC); ONCOGENES; Prognosis; Proliferation; Protein Binding; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Survival Analysis; Tumor Burden; Tumorigenesis; Long noncoding RNA XIST; Tumorigenesis; Proliferation; KLF2; Non-small cell lung cancer (NSCLC)
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.08.030

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. •XIST is up-regulated in human primary NSCLC tissues and cell lines.•Knockdown of XIST represses NSCLC cell proliferation, migration and invasion, in vitro and vivo.•XIST represses KLF2 expression via directly binding with EZH2 in NSCLC cells.•XIST's oncogenic functions are partially through directly binding with EZH2, and then epigenetically repressing KLF2 expression.