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

Silencing of RTKN2 by siRNA suppresses proliferation, and induces G1 arrest and apoptosis in human bladder cancer cells
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DOI:
10.3892/mmr.2016.5127
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发表时间:
2016-06-01
影响因子:
3.4
通讯作者:
Zhang, Xian-Jue
Zhang, Xian-Jue
中科院分区:
医学4区
文献类型:
--
作者:
Liao, Yi-Xiang;Zeng, Jin-Min;Zhang, Xian-Jue

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膀胱癌是我国最常见的泌尿系统恶性肿瘤。基因突变可能是癌症发生的原因之一。因此,本研究调查Rho效应蛋白Rhotekin 2(RTKN 2)在人膀胱癌组织和细胞系中的表达水平,并检查RTKN 2对人膀胱癌细胞系的增殖、细胞周期、凋亡和侵袭的影响。RTKN2 mRNA在30例膀胱癌组织中的表达水平显著高于30例正常膀胱组织。RTKN 2在T24和5637细胞中的蛋白表达水平明显高于其他四种人膀胱癌细胞系。RTKN2的siRNA沉默通过降低T24和5637细胞中的MCM10、CDK2、CDC24A和CDC6细胞周期相关蛋白的表达水平来抑制细胞增殖并将细胞周期阻滞在G1期。此外,RTKN 2在细胞中的敲低导致细胞凋亡和侵袭抑制。这些结果提示RTKN 2参与了人膀胱癌的发生和发展,提示RTKN 2可能成为肿瘤治疗的分子靶点。
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.