Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma
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Wenqiao Zang1, Tao Wang2, Yuanyuan Wang1, Xiaonan Chen1, Yuwen Du1, Qianqian Sun1, Min Li1, Ziming Dong1,3, Guoqiang Zhao1,3
1College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
2Department of Hemato-tumor, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
3Collaborative Innovation Center of Cancer Chemoprevention, Henan, China
Guoqiang Zhao, e-mail: [email protected]
Keywords: LncRNA TP73-AS1, BDH2, biomarker, chemosensitivity, esophageal cancer
Received: July 24, 2015 Accepted: January 13, 2016 Published: January 21, 2016
Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in a variety of biological processes and diseases in humans, including cancer. Our study serves as the first comprehensive analysis of lncRNA TP73-AS1 in esophageal cancer. We utilized a lncRNA microarray to analyze the expression profile of lncRNAs in esophageal squamous cell carcinoma. Our results show that lncRNA TP73-AS1 and BDH2 levels are generally upregulated in esophageal cancer tissues and are strongly correlated with tumor location or TNM stage in clinical samples. LncRNA TP73-AS1 knockdown inhibited BDH2 expression in EC9706 and KYSE30 cells, whereas BDH2 knockdown repressed esophageal cancer cell proliferation and induced apoptosis via the caspase-3 dependent apoptotic pathway. Overexpression of BDH2 in lncRNA TP73-AS1 knockdown cells partially rescued cell proliferation rates and suppressed apoptosis. In mouse xenografts, tumor size was reduced in lncRNA TP73-ASI siRNA-transfected tumors, suggesting that downregulation of lncRNA TP73-AS1 attenuated EC proliferation in vitro and in vivo. In addition, BDH2 or lncRNA TP73-AS1 knockdown enhanced the chemosensitivity of esophageal cancer cells to 5-FU and cisplatin. Our results suggest that lncRNA TP73-AS1 may be a novel prognostic biomarker that could serve as a potential therapeutic target for the treatment of esophageal cancer.
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