The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

Molecular Cancer

Research

Yong-min Li¹  Jia-chen Lv¹  Li Li¹  Yan-long Liu¹  Peng Han¹  Zhi-wei Yu¹  Xue-feng Bai¹  Bo-miao Zhang¹  Yun-he Jia¹  Jing-wen Li¹  Xin-yue Gu¹  Bin-bin Cui¹ 

[1] Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Road, 150040, Harbin, People’s Republic of China;

关键词: CRNDE;    miR-181a-5p;    Wnt/β-catenin signaling;    Colorectal cancer;    Proliferation;    Chemoresistance;   

DOI  :  10.1186/s12943-017-0583-1

 received in 2016-07-06, accepted in 2017-01-03,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWith more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC.MethodsWe examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells.ResultsIn this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/β-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/β-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p.ConclusionsOur study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/β-catenin signaling.

【 授权许可】

CC BY   
© The Author(s). 2017