Overexpression of Reptin in renal cell carcinoma contributes to tumor malignancies and its inhibition triggers senescence of cancer cells
Overexpression of Reptin in renal cell carcinoma contributes to tumor malignancies and its inhibition triggers senescence of cancer cells
复制标题
肾细胞癌中 Reptin 的过度表达导致肿瘤恶性肿瘤，抑制 Reptin 会引发癌细胞衰老
DOI：
10.1016/j.urolonc.2012.01.004
复制
发表时间：
2013-10-01
影响因子：
2.7
通讯作者：
Xu, Zhonghua
中科院分区：
文献类型：
--
作者：
Ren, Juchao;Li, Wenjuan;Xu, Zhonghua
目的：Reptin是一种AAA+ atp酶，与染色质重塑、转录调节、DNA损伤修复和端粒酶活性等多种复合物相关。功能研究表明，reptin参与了许多与癌症高度相关的细胞过程。在这项研究中，我们研究了肾细胞癌（RCC）细胞中reptin的表达及其生物学功能。材料和方法：共有81例RCC患者参与了这项研究。采用免疫组化方法分析癌性及邻近正常肾组织中reptin的表达。使用Kaplan-Meier曲线评估与生存率的单变量关联。特异小干扰RNA抑制了基因表达。分别通过病灶形成、p -半乳糖苷酶染色和流式细胞术检测克隆发生、细胞衰老和细胞周期分布。采用刮刮法和Matrigel法测定细胞的迁移和侵袭能力。结果：与肿瘤邻近肾组织相比，癌组织中Reptin过表达。细胞浆中reptin的表达与RCC分化不良呈正相关，并预示着患者的不良预后。减少reptin表达可显著抑制癌细胞的克隆潜能，诱导RCC细胞衰老。此外，reptin缺失还会减弱RCC细胞在体外的迁移和侵袭能力。结论：Reptin在RCC中存在过表达和异常分布。通过防止细胞生长停滞和衰老，它是癌细胞持续增殖所必需的。此外，reptin促进细胞迁移和侵袭，这可能有助于RCC的进展。因此，reptin可能是预防和治疗肾细胞癌的一个有价值的靶点。(C) 2013爱思唯尔公司版权所有。
Objectives: Reptin is an AAA+ ATPase associated with several complexes involved in chromatin remodeling, transcriptional regulation, DNA damage repair, and telomerase activity. Functional studies have implicated reptin in many cellular processes highly relevant to cancer. In this study, we investigated reptin expression in renal cell carcinoma (RCC) and its biologic functions in RCC cells.Materials and methods: A total of 81 RCC patients were involved in the study. Cancerous and adjacent normal renal tissues were analyzed for reptin expression using immunohistochemistry. Univariate association with survival was evaluated using Kaplan-Meier curves. Gene expression was depleted with specific small interference RNA. Clonogenesis, cellular senescence, and cell cycle distribution were examined by foci formation, P-galactosidase staining, and flow cytometry, respectively. Cell migration and invasion capability were determined by scratch migration assay and Matrigel invasion assay.Results: Reptin is overexpressed in cancerous tissues compared with tumor adjacent renal tissues. Cytoplasmic expression of reptin positively correlates with the poor differentiation of RCC, and predicts an unfavorable outcome for patients. Depleting reptin expression substantially inhibited clonogenic potential of cancer cells and induced senescence of RCC cells. Moreover, reptin depletion attenuated migration and invasion ability of RCC cells in vitro.Conclusions: Reptin is overexpressed and aberrantly distributed in RCC. It is required for sustained proliferation of cancer cells by preventing cell growth arrest and senescence. Furthermore, reptin promotes cell migration and invasion, which may contribute to the progression of RCC. Therefore, reptin may prove to be a valuable target for prevention and treatment of renal cell carcinoma. (C) 2013 Elsevier Inc. All rights reserved.