■透明细胞肾细胞癌(ccRCC)是最常见的肾癌类型,具有高度的异质性和复杂性。最近的研究已经确定线粒体缺陷和自噬是ccRCC发展的关键参与者。本研究旨在探讨ccRCC体内有丝分裂活性的变化及其对肿瘤微环境的影响。揭示其在肿瘤细胞代谢中的作用,发展,和生存策略。
■使用单细胞测序和空间转录组学对ccRCC肿瘤组织进行综合分析,以揭示线粒体自噬在ccRCC中的作用。通过基因集评分确定肾透明细胞中的线粒体自噬发生了改变。使用NMF分析和生存分析方法鉴定关键的线粒体自噬细胞群和关键的预后基因。体外实验也证明了UBB在ccRCC中的作用。
■与正常肾组织相比,ccRCC肿瘤组织内的各种细胞类型表现出显著增加的线粒体自噬水平,尤其是肾透明细胞.与线粒体自噬水平增加相关的关键基因,比如UBC,UBA52,TOMM7,UBB,MAP1LC3B,CSNK2B,被确认,它们的高表达与患者预后不良密切相关。特别是,发现涉及UBB基因的泛素化过程对线粒体自噬及其质量控制至关重要.
■这项研究强调了线粒体自噬及其调节因子在ccRCC发生发展中的核心作用,揭示UBB基因及其相关泛素化过程在疾病进展中的意义。
UNASSIGNED: Clear Cell Renal Cell Carcinoma (ccRCC) is the most common type of kidney cancer, characterized by high heterogeneity and complexity. Recent studies have identified mitochondrial defects and autophagy as key players in the development of ccRCC. This study aims to delve into the changes in mitophagic activity within ccRCC and its impact on the tumor microenvironment, revealing its role in tumor cell metabolism, development, and survival strategies.
UNASSIGNED: Comprehensive analysis of ccRCC tumor tissues using single cell sequencing and spatial transcriptomics to reveal the role of mitophagy in ccRCC. Mitophagy was determined to be altered among renal clear cells by gene set scoring. Key mitophagy cell populations and key prognostic genes were identified using NMF analysis and survival analysis approaches. The role of UBB in ccRCC was also demonstrated by in vitro experiments.
UNASSIGNED: Compared to normal kidney tissue, various cell types within ccRCC tumor tissues exhibited significantly increased levels of mitophagy, especially renal clear cells. Key genes associated with increased mitophagy levels, such as UBC, UBA52, TOMM7, UBB, MAP1LC3B, and CSNK2B, were identified, with their high expression closely linked to poor patient prognosis. Particularly, the ubiquitination process involving the UBB gene was found to be crucial for mitophagy and its quality control.
UNASSIGNED: This study highlights the central role of mitophagy and its regulatory factors in the development of ccRCC, revealing the significance of the UBB gene and its associated ubiquitination process in disease progression.