肾透明细胞癌
癌症研究
肿瘤微环境
细胞生长
免疫系统
基因敲除
生物
细胞
细胞培养
肾细胞癌
医学
病理
免疫学
肿瘤细胞
遗传学
作者
Mingyue Xie,Bo Cheng,Shuang Yu,Yajie He,Yu Cao,Tiejun Zhou,Kun Han,Rongyang Dai,Ronghao Wang
出处
期刊:Cells
[MDPI AG]
日期:2022-12-31
卷期号:12 (1): 173-173
被引量:31
标识
DOI:10.3390/cells12010173
摘要
As a newly identified type of programmed cell death, cuproptosis may have an impact on cancer development, including clear cell renal cell carcinoma (ccRCC). Herein, we first noticed that the expression levels of cuproptosis regulators exhibited a tight correlation with the clinicopathological characteristics of ccRCC. The cuproptosis-sensitive sub-type (CSS), classified via consensus clustering analysis, harbored a higher overall survival rate compared to the cuproptosis-resistant sub-type (CRS), which may have resulted from the differential infiltration of immune cells. FDX1, the cuproptosis master regulator, was experimentally determined as a tumor suppressor in ccRCC cells by suppressing the cell growth and cell invasion of ACHN and OSRC-2 cells in a cuproptosis-dependent and -independent manner. The results from IHC staining also demonstrated that FDX1 expression was negatively correlated with ccRCC tumor initiation and progression. Furthermore, we identified the miR-21-5p/FDX1 axis in ccRCC and experimentally verified that miR-21-5p directly binds the 3′-UTR of FDX1 to mediate its degradation. Consequently, a miR-21-5p inhibitor suppressed the cell growth and cell invasion of ACHN and OSRC-2 cells, which could be compensated by FDX1 knockdown, reinforcing the functional linkage between miR-21-5p and FDX1 in ccRCC. Finally, we evaluated the ccRCC tumor microenvironment under the miR-21-5p/FDX1 axis and noted that this axis was strongly associated with the infiltration of immune cells such as CD4+ T cells, Treg cells, and macrophages, suggesting that this signaling axis may alter microenvironmental components to drive ccRCC progression. Overall, this study constructed the miR-21-5p/FDX1 axis in ccRCC and analyzed its potential impact on the tumor microenvironment, providing valuable insights to improve current ccRCC management.
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