Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer

被引:15
作者
Zhang, Meifeng [1 ]
Wu, Wei [1 ]
Gao, Ming [1 ]
Zhang, Jie [1 ]
Ding, Xinde [1 ]
Zhu, Ronghua [1 ]
Chen, Haiqun [1 ]
Fei, Zhewei [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Xinhua Hosp,Chongming Branch, 25 Nanmen Rd, Shanghai 202150, Peoples R China
关键词
Colorectal cancer; coactivator-associated arginine methyltransferase 1; microRNA-195-5p; proliferation; colony formation; SIGNALING PATHWAYS; ANDROGEN RECEPTOR; LUNG-CANCER; CARM1; EXPRESSION; PROSTATE; PROLIFERATION; METHYLATION; STATISTICS; CARCINOMA;
D O I
10.1177/1010428317694305
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivator-associated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3'-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-1955p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.
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页数:10
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