肾透明细胞癌
生物
基因敲除
癌症研究
转录因子
SOX2
转移
条件基因敲除
癌症
基因
遗传学
肾细胞癌
病理
医学
表型
作者
Chengfang Sun,Jingchao Wei,Zhilin Long,Weixi Zhao,Qi Huangfu,Qi Xie,Bohan Wang,Jiaming Wen
标识
DOI:10.1096/fj.202101310r
摘要
Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of human kidney cancer with a high probability of metastasis. To understand the molecular processing essential for ccRCC tumorigenicity, we conducted an integrative in silico analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset and clustered randomly interspersed short palindromic repeats (CRISPR) screening dataset of ccRCC cell lines from Depmap. We identified spindle pole body component 24 homolog (SPC24) as an essential gene for ccRCC cell lines with prognostic significance in the TCGA database. Targeting SPC24 by CRISPR/Cas9-mediated gene knockout attenuated ccRCC proliferation, metastasis, and in vivo tumor growth. Furthermore, we found that SPC24 regulates metastasis genes expression in a SRY-box transcription factor 2 (SOX2)-dependent manner. The anti-proliferative effects of SPC24 knockout were strengthened with SOX2 knockdown. Collectively, our findings suggest SPC24 has a pivotal function in promoting ccRCC progression, providing a new insight for the treatment of ccRCC.
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