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长链非编码RNA TP73-AS1的敲低抑制食管鳞状细胞癌的细胞增殖并诱导细胞凋亡。

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

作者信息

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

机构信息

College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Department of Hemato-tumor, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China.

出版信息

Oncotarget. 2016 Apr 12;7(15):19960-74. doi: 10.18632/oncotarget.6963.

DOI:10.18632/oncotarget.6963
PMID:26799587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4991431/
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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd42/4991431/592a96464357/oncotarget-07-19960-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd42/4991431/592a96464357/oncotarget-07-19960-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd42/4991431/3ed6034d637d/oncotarget-07-19960-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd42/4991431/ad8c0d0cb879/oncotarget-07-19960-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd42/4991431/ecddd43d3094/oncotarget-07-19960-g003.jpg
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