Mitophagy and clear cell renal cell carcinoma: insights from single-cell and spatial transcriptomics analysis

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Clear Cell Renal Cell Carcinoma (ccRCC) is a complex and heterogeneous kidney cancer.
• Mitochondrial dysfunction and autophagy are implicated in ccRCC development.
• Understanding mitophagy's role in ccRCC is crucial for targeted therapies.

Purpose of the Study:

• To investigate alterations in mitophagy within ccRCC.
• To determine the impact of mitophagy on the tumor microenvironment, metabolism, and survival.
• To identify key genes and cellular pathways involved in ccRCC mitophagy.

Main Methods:

• Single cell sequencing and spatial transcriptomics of ccRCC tissues.
• Gene set scoring to assess mitophagy levels.
• Non-negative Matrix Factorization (NMF) and survival analyses to identify key cell populations and prognostic genes.
• In vitro experiments to validate the role of UBB.

Main Results:

• Mitophagy is significantly elevated in various ccRCC cell types, particularly renal clear cells, compared to normal kidney tissue.
• Key mitophagy-associated genes (UBC, UBA52, TOMM7, UBB, MAP1LC3B, CSNK2B) were identified, with high expression correlating with poor prognosis.
• The ubiquitination process, specifically involving the UBB gene, is critical for mitophagy regulation and quality control in ccRCC.

Conclusions:

• Mitophagy and its regulators play a central role in ccRCC pathogenesis.
• The UBB gene and its ubiquitination pathway are significant drivers of ccRCC progression.
• Targeting mitophagy pathways may offer novel therapeutic strategies for ccRCC.