Zang Wenqiao, Wang Tao, Wang Yuanyuan, Chen Xiaonan, Du Yuwen, Sun Qianqian, Li Min, Dong Ziming, Zhao Guoqiang
College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Department of Hemato-tumor, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China.
Oncotarget. 2016 Apr 12;7(15):19960-74. doi: 10.18632/oncotarget.6963.
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.
最近的研究表明,长链非编码RNA(lncRNA)参与了人类的多种生物学过程和疾病,包括癌症。我们的研究是对食管癌中lncRNA TP73-AS1的首次全面分析。我们利用lncRNA微阵列分析食管鳞状细胞癌中lncRNA的表达谱。我们的结果显示,lncRNA TP73-AS1和BDH2水平在食管癌组织中普遍上调,并且与临床样本中的肿瘤位置或TNM分期密切相关。在EC9706和KYSE30细胞中,lncRNA TP73-AS1敲低抑制了BDH2的表达,而BDH2敲低则通过半胱天冬酶-3依赖性凋亡途径抑制食管癌细胞增殖并诱导凋亡。在lncRNA TP73-AS1敲低的细胞中过表达BDH2可部分挽救细胞增殖率并抑制凋亡。在小鼠异种移植模型中,lncRNA TP73-ASI siRNA转染的肿瘤的肿瘤大小减小,这表明lncRNA TP73-AS1的下调在体外和体内均减弱了食管癌的增殖。此外,BDH2或lncRNA TP73-AS1敲低增强了食管癌细胞对5-氟尿嘧啶和顺铂的化学敏感性。我们的结果表明,lncRNA TP73-AS1可能是一种新型的预后生物标志物,可作为治疗食管癌的潜在治疗靶点。