Wang Hengbing, Li Qi, Niu Xiaobing, Wang Gongcheng, Zheng Sinian, Fu Guangbo, Wang Zengjun
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.
Oncol Lett. 2017 Jan;13(1):435-440. doi: 10.3892/ol.2016.5388. Epub 2016 Nov 16.
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.
微小RNA(miRNA)是一类调控基因表达的小RNA。已证实,miRNA表达异常与癌症发展和致癌作用相关。有人提出,miRNA表达改变在膀胱癌中会出现。在其他癌症系统中,研究表明,作为一种肿瘤抑制基因,miR - 143在癌症进展中发挥着重要作用。然而,其在膀胱癌中的作用尚未阐明。在本研究中,我们观察到miR - 143在人膀胱癌组织和细胞中表达下调,且其水平与膀胱癌临床分期呈负相关。我们进一步证明胰岛素样生长因子 - 1受体(IGF - 1R)是miR - 143的一个功能性靶点。在膀胱癌样本中,它们的表达水平呈负相关。miR - 143的过表达抑制细胞增殖,并促进膀胱癌5637细胞对吉西他滨的化疗敏感性。同样,小干扰RNA介导的IGF - 1R敲低模拟了miR - 143过表达的效果。值得注意的是,IGF - 1R的表达是患者预后的一个预测指标。总体而言,我们的研究结果表明,miR - 143是一种有价值的膀胱癌生物标志物。miR - 143/IGF - 1R轴与膀胱癌耐药性和患者生存率相关。