Sex-Based Differences in Circulating microRNA and Metabolite Signatures Associated with Physical Activity in Lynch...

Area of Science:

• Genetics and Molecular Biology
• Cancer Research
• Metabolomics

Background:

• Lynch syndrome (LS) carriers have elevated cancer risks, particularly colorectal cancer.
• Physical activity (PA) is a known cancer risk modifier, but its sex-specific effects and molecular underpinnings in LS are unclear.

Purpose of the Study:

• To investigate sex-specific molecular mechanisms linking physical activity to cancer-related pathways in Lynch syndrome using an integrated omics approach.

Main Methods:

• Serum microRNAs (miRNAs) profiled via Illumina sequencing and metabolites quantified using NMR in 93 Finnish LS carriers.
• Bioinformatics analyses (PCoA, WGCNA, ORA) explored PA-associated molecular changes.
• Acute exercise response of selected miRNAs was examined.

Main Results:

• Sex-based differences observed in PA-associated circulating miRNAs and metabolites.
• In females, PA linked to lipid metabolism; in males, PA-associated miRNAs regulated cancer-related pathways (cell growth, apoptosis, senescence).
• Four specific miRNAs correlated with lipid/fatty acid metabolism and inflammation markers, with sex-specific patterns; miRNA expression changed post-exercise.

Conclusions:

• Sex is a critical biological factor in PA-based cancer prevention for Lynch syndrome.
• Novel molecular mechanisms, including sex-specific miRNA and metabolic alterations, are associated with PA in LS patients.