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泛素特异性肽酶 19 是一个预后生物标志物,可影响肾透明细胞癌的增殖和迁移。

Ubiquitin specific peptidase 19 is a prognostic biomarker and affect the proliferation and migration of clear cell renal cell carcinoma.

机构信息

Department of Oncology, Huangshi Central Hospital of Edong Healthcare, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei 435000, P.R. China.

Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China.

出版信息

Oncol Rep. 2020 Jun;43(6):1964-1974. doi: 10.3892/or.2020.7565. Epub 2020 Mar 26.

Abstract

Ubiquitin specific peptidase 19 (USP19) is a member of the USP family and exhibits diverse roles in various biological processes, such as cell differentiation, cell cycle progression and apoptosis. There is limited knowledge regarding the role and impact of USP19 in cancer, particularly clear cell renal cell carcinoma (ccRCC). To examine the function of USP19 in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases were examined to determine USP19 mRNA expression levels. USP19 mRNA levels were significantly lower in ccRCC tissues than in normal tissues. USP19 downregulation was associated with ccRCC progression and poor prognostic outcomes in TCGA cohort. Furthermore, the functional involvement of USP19 in ccRCC was examined using Cell Counting Kit‑8, soft agar, Transwell and wound healing assays in vitro following overexpression or knockdown of USP19 in the Caki‑1 cell line. USP19 overexpression inhibited ccRCC proliferation and migration, whereas USP19 knockdown promoted ccRCC proliferation and migration in vitro. Consistent with these results, it was further demonstrated that USP19 downregulation promoted tumor growth in vivo in a xenograft model. Mechanistically, it was found that USP19 exerted its inhibitory effect on ccRCC proliferation and migration by suppressing the activation of ERK. Collectively, the present findings identified a role for USP19 as a tumor suppressor in ccRCC and demonstrated that USP19 is a potential prognostic biomarker that could be applied in ccRCC therapy.

摘要

泛素特异性肽酶 19(USP19)是 USP 家族的一员,在细胞分化、细胞周期进程和细胞凋亡等多种生物学过程中发挥多种作用。目前对于 USP19 在癌症中的作用和影响知之甚少,特别是在透明细胞肾细胞癌(ccRCC)中。为了研究 USP19 在 ccRCC 中的作用,本研究利用癌症基因组图谱(TCGA)和基因表达综合数据库来检测 USP19 mRNA 表达水平。结果发现,ccRCC 组织中的 USP19 mRNA 水平明显低于正常组织。USP19 下调与 TCGA 队列中 ccRCC 的进展和不良预后结局相关。此外,通过在 Caki-1 细胞系中转染 USP19 过表达或敲低载体,利用细胞计数试剂盒-8 检测、软琼脂克隆形成实验、Transwell 检测和划痕愈合实验,在体外进一步研究了 USP19 在 ccRCC 中的功能。USP19 过表达抑制 ccRCC 的增殖和迁移,而 USP19 敲低则促进 ccRCC 的增殖和迁移。与这些结果一致,进一步在异种移植模型中证明了 USP19 下调促进体内肿瘤生长。机制研究发现,USP19 通过抑制 ERK 的激活发挥其对 ccRCC 增殖和迁移的抑制作用。综上所述,本研究结果确定了 USP19 在 ccRCC 中作为肿瘤抑制因子的作用,并表明 USP19 是一种有潜力的预后生物标志物,可应用于 ccRCC 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62e6/7160536/928c7c6d67ac/OR-43-06-1964-g00.jpg

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