miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling

被引:63
|
作者
Wang, Hengbing [1 ,2 ]
Li, Qi [3 ]
Niu, Xiaobing [2 ]
Wang, Gongcheng [2 ]
Zheng, Sinian [2 ]
Fu, Guangbo [2 ]
Wang, Zengjun [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Urol, Huaian 223300, Jiangsu, Peoples R China
[3] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Pathol, Nanjing 210008, Jiangsu, Peoples R China
关键词
miR-143; bladder cancer; gemcitabine; IGF-1R; tumor growth; GROWTH-FACTOR RECEPTOR; BREAST-CANCER; HEXOKINASE; FACTOR-I; TUMOR; MICRORNA-143; PATHWAY; EXPRESSION; CARCINOMA; ANGIOGENESIS;
D O I
10.3892/ol.2016.5388
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages. We further demonstrated that insulin-like growth factor-1 receptor (IGF-1R) is a functional target of miR-143. Their expression levels were inversely correlated in bladder cancer samples. Overexpression of miR-143 inhibited cell proliferation and promoted chemosensitivity of bladder cancer 5637 cells to gemcitabine. Consistently, small interfering RNA-mediated knockdown of IGF-1R phenocopied miR-143 overexpression. Notably, the expression of IGF-1R is a predictor of patient prognosis. Collectively, our findings indicate that miR-143 is a valuable biomarker for bladder cancer. The miR-143/IGF-1R axis is associated with bladder cancer drug resistance and patient survival.
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页码:435 / 440
页数:6
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