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RPN11去泛素化酶促进乳腺癌细胞的增殖和迁移。

RPN11 deubiquitinase promotes proliferation and migration of breast cancer cells.

作者信息

Luo Guoqing, Hu Ningdong, Xia Xu, Zhou Jingjing, Ye Changsheng

机构信息

Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

The First Zone of Cardiothoracic Department, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, P.R. China.

出版信息

Mol Med Rep. 2017 Jul;16(1):331-338. doi: 10.3892/mmr.2017.6587. Epub 2017 May 16.

Abstract

The deubiquitinase enzyme RPN11 is involved in oncogenesis in various types of cancer. However, in breast cancer, the expression levels, prognostic relevance and biological function of RPN11 remains unclear. In the present study, RPN11 expression levels in breast cancer tissues and adjacent non‑tumor tissues were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining, and the association of RPN11 with clinicopathological features of breast cancer was evaluated. RPN11 expression was upregulated in breast cancer tissues compared with healthy tissues. Additionally, high expression levels of RPN11 may be an indicator of poor prognosis, as validated by a breast cancer cohort from the Gene Expression Omnibus database. Knockdown of RPN11 in MDA‑MB‑231 and T47D cells significantly reduced cell proliferation and enhanced G0/G1 arrest and apoptosis. Exogenous overexpression of RPN11 in MCF7 and Hs578T cells promoted cell growth and inhibited apoptosis. In addition, knockdown of RPN11 abrogated cell migration and reduced epithelial‑mesenchymal transition. In conclusion, these findings suggested that RPN11 may function as an oncogene and its upregulation in breast cancer suggests that it may be a therapeutic target.

摘要

去泛素化酶RPN11参与多种类型癌症的肿瘤发生。然而,在乳腺癌中,RPN11的表达水平、预后相关性及生物学功能仍不清楚。在本研究中,通过逆转录-定量聚合酶链反应和免疫组织化学染色测定乳腺癌组织及相邻非肿瘤组织中RPN11的表达水平,并评估RPN11与乳腺癌临床病理特征的相关性。与健康组织相比,乳腺癌组织中RPN11表达上调。此外,如基因表达综合数据库中的乳腺癌队列所证实,RPN11的高表达水平可能是预后不良的一个指标。在MDA-MB-231和T47D细胞中敲低RPN11可显著降低细胞增殖,并增强G0/G1期阻滞和细胞凋亡。在MCF7和Hs578T细胞中外源过表达RPN11可促进细胞生长并抑制细胞凋亡。此外,敲低RPN11可消除细胞迁移并减少上皮-间质转化。总之,这些发现表明RPN11可能作为一种癌基因发挥作用,其在乳腺癌中的上调表明它可能是一个治疗靶点。

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