The Landscape and Regulatory Mechanisms of Aberrant Alternative Splicing Events in Adenomyosis

Aberrant alternative splicing events (AASEs) are associated with numerous diseases; however, little is currently known about AASEs in human adenomyosis, making it essential to understand AS in adenomyosis to clarify its pathogenesis. In this study, we identified 1 022 512 transcripts across transcriptome data from 130 samples (61 adenomyosis patients and 69 controls), including 483 629 novel transcripts not annotated in the reference genome. Additionally, 229236 ASEs were identified, of which 531 were classified as AASEs. Furthermore, we constructed a network of 13 differentially expressed RNA-binding proteins (RBPs) regulating 226 AASEs. Through cis-sQTL (cis-acting Splicing Quantitative Trait Locus) analysis, 14629 sQTLs were detected. Enrichment analysis of the genes containing these sQTLs suggests that their functions are involved in uterine-related disease regulation processes. Moreover, a statistically significant single-nucleotide polymorphism (SNP) (chr4:173588365, P-adjust < 0.05) was identified within lncRNA HAND2-AS1, which is significantly associated with its AS. HAND2-AS1 has been reported to regulate the proliferative capacity and migratory potential of endometrial stromal cells – processes closely linked to the pathogenesis of endometriosis. The results of this study enhance our understanding of the mechanism of AS in adenomyosis and provide a new perspective for further research on adenomyosis.