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泛素特异性肽酶 39 的敲低抑制了人肾细胞癌的恶性进展。

Knockdown of ubiquitin‑specific peptidase 39 inhibits the malignant progression of human renal cell carcinoma.

机构信息

Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.

Department of Urology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China.

出版信息

Mol Med Rep. 2018 Mar;17(3):4729-4735. doi: 10.3892/mmr.2018.8421. Epub 2018 Jan 11.

DOI:10.3892/mmr.2018.8421
PMID:29328477
Abstract

Ubiquitin specific peptidase 39 (USP39) serves important roles in mRNA processing and is involved in tumorigenesis of multiple solid malignancies. However, the influence and underlying mechanism of USP39 on human renal cell carcinomas (RCC) remain to be elucidated. The current study investigated the functional roles of USP39 in human RCC cell lines. siRNA‑mediated RNA interference was used to downregulate USP39 in RCC cells. CCK‑8, wound healing and invasion assays were performed to assess the proliferative ability and metastatic potential. The cell cycle distribution and apoptosis were evaluated by flow cytometry. The activity of signaling pathways and the expression of cell cycle‑related proteins were detected by western blot analysis. The siRNA‑directed RNA interference targeting USP39 could effectively downregulate the expression level of USP39 in two RCC cell lines. Depletion of USP39 by siRNA significantly suppressed cell growth and decreased invasive capacity of RCC cells. Silencing of USP39 induced cell apoptosis and cell cycle arrest at G2/M phase. Additionally, the expression levels of apoptotic and G2/M phase‑related proteins were notably decreased following depletion of USP39. Mechanistically, downregulation of USP39 blocked the activation of Akt and extracellular signal regulated kinase signaling pathways in RCC cells. These findings indicate that USP39 may serve as an oncogenic factor in RCC and could be a potential therapeutic candidate for human RCCs.

摘要

泛素特异性肽酶 39(USP39)在 mRNA 处理中发挥重要作用,并且参与多种实体恶性肿瘤的发生。然而,USP39 对人肾细胞癌(RCC)的影响及其潜在机制仍有待阐明。本研究旨在探讨 USP39 在人 RCC 细胞系中的功能作用。采用 siRNA 介导的 RNA 干扰技术下调 RCC 细胞中的 USP39。通过 CCK-8 法、划痕愈合实验和侵袭实验评估细胞的增殖能力和转移潜能。通过流式细胞术评估细胞周期分布和细胞凋亡。通过 Western blot 分析检测信号通路的活性和细胞周期相关蛋白的表达。靶向 USP39 的 siRNA 可有效下调两种 RCC 细胞系中 USP39 的表达水平。siRNA 介导的 USP39 耗竭显著抑制 RCC 细胞的生长和侵袭能力。沉默 USP39 诱导细胞凋亡并使细胞周期停滞在 G2/M 期。此外,USP39 耗竭后凋亡和 G2/M 期相关蛋白的表达水平显著降低。机制上,USP39 的下调阻断了 RCC 细胞中 Akt 和细胞外信号调节激酶信号通路的激活。这些发现表明,USP39 可能是人 RCC 的致癌因子,并且可能是治疗人 RCC 的潜在候选药物。

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