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下调的假基因CTNNAP1通过下调其同源基因CTNNA1的表达促进人类癌症中的肿瘤生长。

Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by downregulating its cognate gene CTNNA1 expression.

作者信息

Chen Xiangjian, Zhu Hua, Wu Xiaoli, Xie Xuemeng, Huang Guanli, Xu Xiaoqun, Li Shi, Xing Chungen

机构信息

Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.

Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.

出版信息

Oncotarget. 2016 Aug 23;7(34):55518-55528. doi: 10.18632/oncotarget.10833.

Abstract

Accumulating evidence indicates that deregulation of cancer-associated pseudogene is involved in the pathogenesis of cancer. In the study, we demonstrated that pseudogene CTNNAP1, for the CTNNA1 gene, was dysregulated in colorectal cancer and the degree of dysregulation was remarkably associated with tumor node metastasis (TNM) stage (P<0.05). The mechanistic experiments revealed that pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene CTNNA1 by competition for microRNA-141. Moreover, gain-of-function approaches showed that overexpression of CTNNAP1 or CTNNA1 significantly inhibited cell proliferation and tumor growth in vitro and in vivo by inducing G0/G1 cell cycle arrest. Our findings add a new regulatory circuit via competing endogenous RNA (ceRNA) cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1, and provide new insights into potential diagnostic biomarker for monitoring human colorectal cancer.

摘要

越来越多的证据表明,癌症相关假基因的失调参与了癌症的发病机制。在本研究中,我们证明了CTNNA1基因的假基因CTNNAP1在结直肠癌中表达失调,且失调程度与肿瘤淋巴结转移(TNM)分期显著相关(P<0.05)。机制实验表明,假基因CTNNAP1通过竞争微小RNA-141在其同源基因CTNNA1的调控中起关键作用。此外,功能获得性实验表明,CTNNAP1或CTNNA1的过表达通过诱导G0/G1期细胞周期阻滞在体外和体内显著抑制细胞增殖和肿瘤生长。我们的研究结果通过假基因CTNNAP1与其同源基因CTNNA1之间的竞争性内源RNA(ceRNA)相互作用增加了一个新的调控回路,并为监测人类结直肠癌的潜在诊断生物标志物提供了新的见解。

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