Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells.
Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells.
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敲低 Rhotekin 2 表达可抑制结肠癌细胞增殖并诱导细胞凋亡
DOI：
10.3892/ol.2017.7182
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发表时间：
2017-12
期刊：
影响因子：
2.9
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Pang X;Li R;Shi D;Pan X;Ma C;Zhang G;Mu C;Chen W
结肠癌是人体最常见的恶性肿瘤之一，在胃肠道肿瘤中排名第二。它在欧洲、美洲和中国的发病率很高，全球每年报告的结肠癌新发病例超过100万例。我国结肠癌发病率从20世纪70年代初的12/10万上升到目前的56/10万，年增长率为4.2%，远远超过国际水平（2%）。Rhotekin（RTKN）2是一种Rho-鸟苷三磷酸酶（GTdR）效应物，据报道具有抗凋亡作用。然而，RTKN 2在结肠癌中的生物学功能的分子机制仍然未知。本研究调查了RTKN 2的mRNA表达水平是否在30例人结肠癌标本中显著高于癌旁组织。结果显示，RTKN 2在SW 480和HCT 116细胞中的蛋白表达水平明显高于HIEC细胞。通过慢病毒介导的RNA干扰敲低SW 480和HCT 116结肠癌细胞中的RTKN 2，通过降低PCDA、Cyclin D1和c-myc细胞周期相关蛋白的表达水平，导致细胞增殖和细胞周期进展的显著抑制。RTKN 2沉默对结肠癌细胞增殖的抑制作用可能部分通过抑制Wnt/β-catenin信号通路实现。RTKN 2基因沉默可通过降低Bax的表达水平和增加Bcl 2的表达水平诱导细胞凋亡。这些结果表明RTKN 2参与了人类结肠癌的发生和发展，表明RTKN 2可能是结肠癌治疗的分子靶点。
Colon cancer is one of the most common malignant tumors in the human body, ranking second as a gastrointestinal tumor. It has a high incidence in Europe, America and China and more than 1 million new cases of colon cancer are reported worldwide each year. The incidence of colon cancer in China has increased from 12/0.1 million in the early 1970s to 56/0.1 million at present with an annual growth rate of 4.2%, which far exceeds the international level (2%). Rhotekin (RTKN) 2, a Rho-guanosine triphosphatase (GTPase) effector, has been reported to be anti-apoptotic. However, the molecular mechanism underlying the biological function of RTKN2 in colon cancer remains unknown. The present study investigated whether the mRNA expression level of RTKN2 was markedly higher in 30 human colon cancer specimens compared with adjacent non-cancerous tissues. The results showed that the protein expression level of RTKN2 was significantly higher in SW480 and HCT116 cells, compared with HIEC cells. Knockdown of RTKN2 in the SW480 and HCT116 colon cancer cells, by lentivirus-mediated RNA interference led to the notable inhibition of cell proliferation and cell cycle progression, by reducing the expression levels of the PCDA, Cyclin D1 and c-myc cell cycle-associated proteins. The inhibitory effect of RTKN2 silencing on the proliferation of colon cancer cells may be partially realized by inhibiting the Wnt/β-catenin signaling pathway. Furthermore, the silencing of RTKN2 in the cells induced apoptosis by reducing the expression level of Bax and increasing the expression level of Bcl2. These results show that RTKN2 is involved in the carcinogenesis and progression of human colon cancer, indicating that RTKN2 may be a molecular target in colon cancer therapy.
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影响因子：
5.2
作者：
Wang, Shihua;Bian, Chunjing;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
1.1
作者：
Wilkes, Gail M
通讯作者：
Wilkes, Gail M
影响因子：
2.8
作者：
AUPEIX, K;WELTIN, D;BISCHOFF, P
通讯作者：
BISCHOFF, P
影响因子：
8
作者：
Chen, M.;Bresnick, A. R.;O'Connor, K. L.
通讯作者：
O'Connor, K. L.
影响因子：
3.4
作者：
Liao, Yi-Xiang;Zeng, Jin-Min;Zhang, Xian-Jue
通讯作者：
Zhang, Xian-Jue