miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1

Molecular Cancer

Research

Zhijian Liu¹  Feng Sun¹  Jing Li²  Chenyu Zhang²  Xi Chen²  Rongjie Cheng²  Shufang Cui²  Chao Ye²  Zheng Fu²  Yanqing Liu²  Xiaorui Chen²  Yuanyuan Gu²  Fei Yang²  Yanbo Wang²  Wu Sun³  Chaoying You³  Rui Liu³ 

[1] Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 321 Zhongshan Road, 210008, Nanjing, Jiangsu, China;State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, 210046, Nanjing, Jiangsu, China;Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, 300060, Tianjin, China;

关键词: Colorectal cancer;    microRNA;    miR-19a;    TIA1;   

DOI  :  10.1186/s12943-017-0625-8

 received in 2016-10-31, accepted in 2017-02-26,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated.MethodsIn CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model.ResultsIn colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3’-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1.ConclusionsThis study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.

【 授权许可】

CC BY   
© The Author(s). 2017