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

被引:157
作者
Liu, Yanqing [1 ]
Liu, Rui [2 ]
Yang, Fei [1 ]
Cheng, Rongjie [1 ]
Chen, Xiaorui [1 ]
Cui, Shufang [1 ]
Gu, Yuanyuan [1 ]
Sun, Wu [2 ]
You, Chaoying [2 ]
Liu, Zhijian [3 ]
Sun, Feng [3 ]
Wang, Yanbo [1 ]
Fu, Zheng [1 ]
Ye, Chao [1 ]
Zhang, Chenyu [1 ]
Li, Jing [1 ]
Chen, Xi [1 ]
机构
[1] Nanjing Univ, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, Collaborat Innovat Ctr Chem Life Sci, NJU Adv Inst Life Sci NAILS,State Key Lab Pharmac, 163 Xianlin Rd, Nanjing 210046, Jiangsu, Peoples R China
[2] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China
[3] Nanjing Med Univ, Nanjing Drum Tower Hosp, Clin Coll, Dept Gastrointestinal Surg, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Colorectal cancer; microRNA; miR-19a; TIA1; RENAL-CELL CARCINOMA; SMRNA-SEQ DATABASE; MESSENGER-RNA; C-MYC; MESENCHYMAL TRANSITION; MICRORNA; METASTASIS; BINDING; EXPRESSION; CLUSTER;
D O I
10.1186/s12943-017-0625-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Colorectal 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. Methods: In 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. Results: In 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. Conclusions: This 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.
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页数:17
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