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通过小干扰RNA(siRNA)使RTKN2沉默可抑制人膀胱癌细胞的增殖,并诱导G1期阻滞和细胞凋亡。

Silencing of RTKN2 by siRNA suppresses proliferation, and induces G1 arrest and apoptosis in human bladder cancer cells.

作者信息

Liao Yi-Xiang, Zeng Jin-Min, Zhou Jia-Jie, Yang Guang-Hua, Ding Kun, Zhang Xian-Jue

机构信息

Department of Urology, Jingzhou Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jingzhou, Hubei 434020, P.R. China.

出版信息

Mol Med Rep. 2016 Jun;13(6):4872-8. doi: 10.3892/mmr.2016.5127. Epub 2016 Apr 14.

Abstract

Human bladder cancer is the most common urological malignancy in China. One of the causes of carcinogenesis in the cancer may be gene mutation. Therefore, the present study investigated the expression levels of Rhotekin 2 (RTKN2), a Rho effector protein, in human bladder cancer tissues and cell lines, and examined the effect of RTKN2 on the proliferation, cell cycle, apoptosis and invasion of human bladder cancer cell lines. The mRNA expression levels of RTKN2 in 30 human bladder cancer tissue samples were significantly higher, compared with those in 30 normal human bladder tissue samples. The protein expression levels of RTKN2 was markedly higher in T24 and 5637 cells, compared with those in four other human bladder cancer cell lines. The silencing of RTKN2 by small interfering (si)RNA inhibited cell proliferation and arrested cell cycle at the G1 phase, via reducing the expression levels of the MCM10, CDK2, CDC24A and CDC6 cell cycle‑associated proteins in the T24 and 5637 cells. Furthermore, RTKN2 knockdown in the cells led to cell apoptosis and the suppression of invasion. These results suggested that RTKN2 is involved in the carcinogenesis and progression of human bladder cancer, indicating that RTKN2 may be a molecular target in cancer therapy.

摘要

膀胱癌是中国最常见的泌尿系统恶性肿瘤。该癌症发生的原因之一可能是基因突变。因此,本研究调查了Rho效应蛋白Rhotekin 2(RTKN2)在人膀胱癌组织和细胞系中的表达水平,并检测了RTKN2对人膀胱癌细胞系增殖、细胞周期、凋亡及侵袭的影响。与30例正常人膀胱组织样本相比,30例人膀胱癌组织样本中RTKN2的mRNA表达水平显著更高。与其他4种人膀胱癌细胞系相比,T24和5637细胞中RTKN2的蛋白表达水平明显更高。小干扰(si)RNA沉默RTKN2可抑制细胞增殖,并使细胞周期停滞于G1期,这是通过降低T24和5637细胞中与细胞周期相关的MCM10、CDK2、CDC24A和CDC6蛋白的表达水平实现的。此外,细胞中RTKN2表达下调导致细胞凋亡及侵袭受抑制。这些结果表明,RTKN2参与了人膀胱癌的发生和进展,提示RTKN2可能是癌症治疗的一个分子靶点。

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