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CORO6通过激活WNT信号通路促进肾透明细胞癌的细胞生长和侵袭。

CORO6 Promotes Cell Growth and Invasion of Clear Cell Renal Cell Carcinoma via Activation of WNT Signaling.

作者信息

Wang Xinjun, Xiao Yiming, Li Si, Yan Zhijian, Luo Guangcheng

机构信息

Department of Urology, Zhongshan Hospital Xiamen University, Xiamen, China.

The School of Clinical Medicine, Fujian Medical University, Fujian, China.

出版信息

Front Cell Dev Biol. 2021 May 7;9:647301. doi: 10.3389/fcell.2021.647301. eCollection 2021.

Abstract

Renal cell carcinoma (RCC) constitutes the most lethal type of genitourinary cancer. Understanding of RCC tumor biology helps to identify novel targets and develop directed treatments for patients with this type of cancer. Analysis from both The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and our RCC samples demonstrated that the expression level of CORO6 was significantly higher in RCC patients than in normal kidney tissues, and its level was highly associated with tumor stage and grade. Importantly, CORO6 expression level was an independent predictor of tumor metastasis and overall survival in RCC patients. Our cell line data also confirmed that CORO6 knockdown could suppress RCC cell growth as well as cell migration and invasion. The depletion of CORO6 led to cell cycle arrest at the G0/G1 phase and caused cell apoptosis. Further, mechanistic dissection showed that CORO6 mediated RCC cell growth, and cell invasion relied on WNT signaling. Moreover, the data suggested that CORO6 knockdown indeed suppressed RCC tumor growth. Overall, our study defines the oncogenic role of CORO6 in RCC progression and provides a rationale for developing CORO6-targeted therapies for improved treatment of RCC patients.

摘要

肾细胞癌(RCC)是泌尿生殖系统癌症中最致命的类型。了解RCC肿瘤生物学有助于识别新的靶点,并为这类癌症患者开发针对性的治疗方法。来自癌症基因组图谱肾透明细胞癌数据集以及我们的RCC样本的分析表明,CORO6在RCC患者中的表达水平显著高于正常肾组织,且其水平与肿瘤分期和分级高度相关。重要的是,CORO6表达水平是RCC患者肿瘤转移和总生存期的独立预测指标。我们的细胞系数据也证实,敲低CORO6可抑制RCC细胞的生长以及细胞迁移和侵袭。CORO6的缺失导致细胞周期停滞在G0/G1期并引起细胞凋亡。此外,机制分析表明,CORO6介导RCC细胞生长,细胞侵袭依赖于WNT信号通路。而且,数据表明敲低CORO6确实抑制了RCC肿瘤生长。总体而言,我们的研究确定了CORO6在RCC进展中的致癌作用,并为开发针对CORO6的疗法以改善RCC患者的治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a275/8137982/53637f4cac9f/fcell-09-647301-g0001.jpg

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