Cancer-associated mutational patterns reshape miRNA regulatory regions and potentially disrupt miRNA-gene...

MicroRNAs (miRNAs) are key post-transcriptional regulators frequently dysregulated in cancer, yet how somatic mutational patterns influence miRNA regulatory regions remains unclear. In this study, we integrated mutation profiles, transition-transversion (Ti/Tv) ratios, and miRNA-gene interaction analyses across multiple TCGA cancer subtypes to investigate how mutation patterns may affect miRNA binding regions. miRNA interactions were strongly enriched in 3' untranslated regions (3'UTRs), with fewer interactions observed in coding sequences (CDS). Across cancers, miRNA regions exhibited moderate GC content (~51%), which typically predicts elevated Ti/Tv ratios; however, most cancer cohorts showed markedly reduced Ti/Tv ratios, indicating a shift toward transversion-heavy mutational processes. Because transversions generally produce greater nucleotide class changes than transitions, this shift may increase the likelihood of disrupting sequence-specific miRNA binding. Supporting this, we identified missense mutations overlapping predicted miRNA binding sites within coding regions, highlighting a potential intersection between somatic mutations and post-transcriptional regulation. Together, these findings suggest that cancer-associated mutational patterns may reshape miRNA regulatory regions and alter miRNA-gene interactions, providing insight into how somatic mutations impact gene regulation beyond protein-coding changes.