Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression
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Fengqi Nie1,*, Xiang Yu2,*, Mingde Huang3,*, Yunfei Wang4, Min Xie5, Hongwei Ma6, Zhaoxia Wang1, Wei De5 and Ming Sun4
1Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China
2Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, People’s Republic of China
3Department of Medical Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, People’s Republic of China
4Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA
5Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People’s Republic of China
6Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
*These authors contributed equally to this work and should be regarded as joint first authors
Ming Sun, email: [email protected]
Zhaoxia Wang, email: [email protected]
Wei De, email: [email protected]
Keywords: long noncoding RNA, ZFAS1, gastric cancer, proliferation, KLF2 and NKD2
Received: February 10, 2016 Accepted: May 02, 2016 Published: May 26, 2016
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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