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RPS20 表达在肾透明细胞癌中的生化和临床效应。

Biochemical and clinical effects of RPS20 expression in renal clear cell carcinoma.

机构信息

Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

出版信息

Oncol Rep. 2023 Jan;49(1). doi: 10.3892/or.2022.8459. Epub 2022 Dec 9.

DOI:10.3892/or.2022.8459
PMID:36484407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9773015/
Abstract

Renal cell carcinoma (RCC) remains one of the most lethal urinary tumors in East Asia despite great advancements in treatment strategies in recent years. Ribosomal protein S20 (RPS20) is considered a new oncogene; however, little information is available on its expression, regulation and biological function in patients with RCC. In the present study, 43 pairs of human RCC and neighboring normal renal tissues were examined for protein expression and immunohistochemistry examination of RPS20. Lentiviral transduction was also employed to create RPS20 knockdown cell lines for downstream cellular experiments. MTT, flow cytometry, wound healing, colony formation and invasion assays were used to examine how RPS20 affected kidney renal clear cell carcinoma (KIRC) cell behavior. Western blotting was used to detect cycle‑related proteins (CDK4 and cyclin D1), Wnt‑related proteins (N‑cadherin and E‑cadherin) and signaling proteins [phosphorylated (p)‑AKT and p‑ERK]. The functions of RPS20 were examined in 786‑O cells with RPS20 knockdown. RPS20 was significantly overexpressed in tumor tissues compared with its expression in the corresponding normal tissues. RPS20 expression was linked to tumor stage, differentiation grade, tumor size and lymph node metastasis, and it had an independent prognostic value in KIRC. Since RCC cell proliferation, migration and invasion were suppressed when RPS20 was knocked down, the formation of renal tumors was markedly slowed down. In RPS20 knockdown cell lines, CDK4, cyclin D1 and E‑cadherin were downregulated, while N‑cadherin expression was increased. RPS20 was also observed to be involved in controlling the activation of the ERK and mTOR signaling pathways. In summary, the present study showed that RPS20 increased cell proliferation in RCC by activating the AKT‑mTOR and ERK‑MAPK signaling pathways, which suggests that RPS20 may be a therapeutic and prognostic target for RCC.

摘要

肾细胞癌(RCC)仍然是东亚最致命的泌尿系统肿瘤之一,尽管近年来治疗策略取得了重大进展。核糖体蛋白 S20(RPS20)被认为是一种新的癌基因;然而,关于其在 RCC 患者中的表达、调节和生物学功能的信息很少。在本研究中,检查了 43 对人 RCC 及其邻近正常肾组织中的 RPS20 蛋白表达和免疫组织化学。还使用慢病毒转导创建了 RPS20 敲低细胞系,用于下游细胞实验。MTT、流式细胞术、划痕愈合、集落形成和侵袭实验用于研究 RPS20 如何影响肾透明细胞癌(KIRC)细胞行为。Western blot 用于检测细胞周期相关蛋白(CDK4 和 cyclin D1)、Wnt 相关蛋白(N-钙粘蛋白和 E-钙粘蛋白)和信号蛋白[磷酸化(p)-AKT 和 p-ERK]。在 786-O 细胞中用 RPS20 敲低检查了 RPS20 的功能。与相应正常组织相比,RPS20 在肿瘤组织中显著过表达。RPS20 的表达与肿瘤分期、分化程度、肿瘤大小和淋巴结转移有关,在 KIRC 中具有独立的预后价值。由于敲低 RPS20 抑制了 RCC 细胞的增殖、迁移和侵袭,因此肾肿瘤的形成明显减慢。在 RPS20 敲低细胞系中,CDK4、cyclin D1 和 E-钙粘蛋白下调,而 N-钙粘蛋白表达增加。还观察到 RPS20 参与控制 ERK 和 mTOR 信号通路的激活。总之,本研究表明,RPS20 通过激活 AKT-mTOR 和 ERK-MAPK 信号通路增加 RCC 中的细胞增殖,这表明 RPS20 可能是 RCC 的治疗和预后靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/9cb5b8a02df3/or-49-01-08459-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/32149334b090/or-49-01-08459-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/c3f2229ab86f/or-49-01-08459-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/4fcf64015275/or-49-01-08459-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/1029145c2936/or-49-01-08459-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/826ed4347cc3/or-49-01-08459-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/f61396bb60d3/or-49-01-08459-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/6ae574e74dc7/or-49-01-08459-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/913f54ccfb5d/or-49-01-08459-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/9cb5b8a02df3/or-49-01-08459-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/32149334b090/or-49-01-08459-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/c3f2229ab86f/or-49-01-08459-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/4fcf64015275/or-49-01-08459-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/1029145c2936/or-49-01-08459-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/826ed4347cc3/or-49-01-08459-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/f61396bb60d3/or-49-01-08459-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/6ae574e74dc7/or-49-01-08459-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/913f54ccfb5d/or-49-01-08459-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e51/9773015/9cb5b8a02df3/or-49-01-08459-g08.jpg

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