MeRIP-seq data analysis and validation reveal the regulatory role of m⁶A modified circRNAs in the apoptosis of secondary hair follicle cells in Inner Mongolia cashmere goats

As a widely epigenetic modification, m⁶A (N⁶-methyladenosine, m⁶A) can regulate the degradation, translation, and other biological functions of circRNAs through dynamic reversible processes. It plays an important role in regulating the life activities of biological organisms, particularly in cell differentiation, apoptosis, embryonic development, stress response, and innate immunity. In this study, bioinformatics analysis, qRT-PCR identification, FISH subcellular localization, and ceRNA network construction were performed on m⁶A modified circRNAs regulating the apoptosis of secondary hair follicle cells of Inner Mongolia Albas white cashmere goats based on the skin m⁶A sequencing data of secondary hair follicles in anagen and catagen. The results showed that 8 m⁶A modified circRNAs regulating the cell apoptosis of secondary hair follicles, namely circRNA_2130, circRNA_0013, circRNA_1203, circRNA_1462, circRNA_1242, circRNA_2308, circRNA_2654 and circRNA_1442 were identified, and they are respectively derived from ANGEL2, APP, GKAP1, HNRNPC, PTBP3, NUCB1, SNRK and ZNF609 genes. Among them, circRNA_0013, circRNA_1442 and circRNA_1462 were located in the cytoplasm of the secondary hair follicle papilla, while circRNA_1203, circRNA_1242, circRNA_2130, circRNA_2308 and circRNA_2654 were located in the nucleus. There are complex and diverse regulatory relationships among 8 circRNAs, with each circRNA targeting one or more miRNAs, revealing that each m⁶A circRNA can exert regulatory effects through multiple potential miRNA-mRNA axes, to regulate the apoptosis of secondary hair follicle cells of cashmere goats during the growth cycles. This result provides a direction for further elucidating the regulatory mechanism of m⁶A modified circRNAs in cashmere growth and exploring biomarkers.