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

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.

Oncology letters. 2016 Nov 16 [Epub]

Hengbing Wang, Qi Li, Xiaobing Niu, Gongcheng Wang, Sinian Zheng, Guangbo Fu, Zengjun Wang

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China; Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China., Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China., Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China., Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

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