Regulator of cullins-1 predicts a poor prognosis and regulates epithelial-mesenchymal transition process through GSK-3β/Wnt signaling in renal cell carcinoma.

IF 1.9 3区 医学 Q4 ANDROLOGY
Translational andrology and urology Pub Date : 2025-04-30 Epub Date: 2025-04-27 DOI:10.21037/tau-2024-646
Qi Wu, Peng Li, Huijiang Zhang, Shengjie You, Zhaoyu Xu, Xiang Liu, Xuedong Chen, Weili Zhang, Xiaoqing Zhou
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引用次数: 0

Abstract

Background: Renal cell carcinoma (RCC) exhibits malignant biological characteristics of cell invasion and metastasis. The role of regulator of cullins-1 (ROC1) in RCC is unknown. The present work focused on exploring ROC1's biological effect on RCC as well as clarifying its related mechanism.

Methods: The messenger RNA (mRNA) expression of ROC1 in RCC tumor tissue and normal tissue was examined by reverse transcription-polymerase chain reaction (RT-PCR). We analyzed mRNA expression through RT-PCR, whereas protein level via western blot (WB) assay. We did some biological experiments in this study, including Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, Transwell invasion assay, and xenograft tumor assay.

Results: ROC1 expression markedly increased in the RCC samples relative to healthy samples. ROC1 was related to the dismal outcome of RCC patients. We also found that the overexpression of ROC1 (oeROC1) promoted cell proliferation, epithelial-mesenchymal transition (EMT), and invasion, whereas ROC1 interference had opposite effects. ROC1 regulated GSK-3β/Wnt pathway within RCC cells. By constructing the RCC metastasis model in nude mice, it was found that ROC1 knockdown inhibited tumor metastasis, while shGSK-3β could reverse the effect of ROC1 knockdown.

Conclusions: Collectively, our work preliminarily illuminated the tumor-promoting role of ROC1 in RCC and the potential molecular mechanism. Thus, our study may provide some evidence for the treatment of RCC.

cullins-1的调节因子可预测肾细胞癌的不良预后,并通过GSK-3β/Wnt信号传导调节上皮-间质转化过程。
背景:肾细胞癌(RCC)具有细胞侵袭和转移的恶性生物学特征。cullins-1调节因子(ROC1)在RCC中的作用尚不清楚。本文主要探讨ROC1在RCC中的生物学作用,并阐明其相关机制。方法:采用逆转录聚合酶链反应(RT-PCR)检测RCC肿瘤组织和正常组织中ROC1 mRNA的表达。我们通过RT-PCR分析mRNA的表达,通过western blot (WB)检测蛋白质水平。在本研究中,我们做了一些生物学实验,包括细胞计数试剂盒-8 (CCK-8)、5-乙基-2'-脱氧尿苷(EdU)、Transwell侵袭试验和异种移植肿瘤试验。结果:RCC细胞中ROC1的表达明显高于正常细胞。ROC1与RCC患者预后不良有关。我们还发现,过表达ROC1 (oeROC1)可促进细胞增殖、上皮-间质转化(EMT)和侵袭,而干扰ROC1则具有相反的作用。ROC1调控RCC细胞GSK-3β/Wnt通路。通过构建裸鼠RCC转移模型,发现ROC1敲低可抑制肿瘤转移,而shGSK-3β可逆转ROC1敲低的作用。结论:我们的工作初步阐明了ROC1在RCC中的促瘤作用及其可能的分子机制。因此,我们的研究可能为RCC的治疗提供一些依据。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
80
期刊介绍: ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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