ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism

Area of Science:

• Oncology
• Genetics
• Cell Biology
• Metabolomics

Background:

• Prostate cancer (PrCa) is a leading global cancer in males, with genetic factors significantly influencing risk.
• Identifying aggressive PrCa cases early is crucial for effective treatment and avoiding overtreatment.
• Germline variants in ANO7 have been previously associated with aggressive PrCa, but its function in prostate cells was unknown.

Purpose of the Study:

• To investigate the functional role of ANO7 in prostate cells.
• To understand how ANO7 expression affects cellular metabolism and lipid profiles.
• To explore ANO7's potential as a biomarker for aggressive PrCa.

Main Methods:

• RNA-sequencing (RNA-seq) and single-cell RNA-sequencing (scRNA-seq) of engineered prostate cells and tissues.
• Differential gene expression and gene set enrichment analysis (GSEA) to identify affected pathways.
• Assays for oxidative phosphorylation (OXPHOS), glycolysis, targeted metabolomics, mitochondrial morphology, and lipidomics.

Main Results:

• ANO7 expression downregulated MYC pathway and OXPHOS genes, shifting metabolism towards glycolysis.
• Reduced aspartate levels and altered mitochondrial morphology indicated disrupted mitochondrial function.
• ANO7 affected lipid metabolism, altering cellular lipid composition with longer acyl chains and increased unsaturation.

Conclusions:

• ANO7 plays a significant role in regulating prostate cell metabolism, particularly OXPHOS and lipid metabolism.
• The study elucidates a previously unknown function of ANO7 in modulating mitochondrial function and lipid profiles.
• Findings provide a foundation for understanding ANO7's role in PrCa aggressiveness and potential biomarker development.