Journal
ONCOTARGET
Volume 8, Issue 24, Pages 38227-38238Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9611
Keywords
long noncoding RNA; ZFAS1; gastric cancer; proliferation; KLF2 and NKD2
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Funding
- National Natural Science Foundation of China [81272601, 81472198]
- Key Clinical Medicine Technology Foundation of Jiangsu Province [BL2014096]
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Recently, long noncoding RNAs have been emerged as critical regulators of human disease and prognostic markers in several cancers, including gastric cancer. In this study, we globally assessed the transcriptomic differences of lncRNAs in gastric cancer using publicly available microarray data from Gene Expression Omnibus (GEO) and identified an oncogenetic lncRNA ZFAS1, which may promote gastric tumorigenesis. ZFAS1 has been found to be upregulated and function as oncogene in colorectal cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in gastric cancer is still undetermined. Here, we reported that ZFAS1 expression is also overexpressed in gastric cancer, and its increased level is associated with poor prognosis and shorter survival. Knockdown of ZFAS1 impaired gastric cancer cells proliferation and induced apoptosis in vitro, and inhibited tumorigenicity of gastric cancer cells in vivo. Mechanistically, RNA immunoprecipitation and RNA pull-down experiment showed that ZFAS1 could simultaneously interact with EZH2 and LSD1/CoREST to repress underlying targets KLF2 and NKD2 transcription. In addition, rescue experiments determined that ZFAS1 oncogenic function is partly dependent on repressing KLF2 and NKD2. Taken together, our findings illuminate how ZFAS1 over-expression confers an oncogenic function in gastric cancer.
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