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Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma

Wenqiao Zang _, Tao Wang, Yuanyuan Wang, Xiaonan Chen, Yuwen Du, Qianqian Sun, Min Li, Ziming Dong and Guoqiang Zhao

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Oncotarget. 2016; 7:19960-19974. https://doi.org/10.18632/oncotarget.6963

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Abstract

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

Correspondence to:

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

ABSTRACT

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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