The development of secondary hair follicles in cashmere goats directly influences the yield and quality of cashmere, and hair follicle morphogenesis is a complex biological process involving multiple signaling pathways and regulatory factors. In recent years, the regulatory role of long non-coding RNAs in hair follicle development has gradually been uncovered. Based on a previously established transcriptome database of embryonic skin tissue from cashmere goats, this study ultimately identified lncRNA MRPS28, which exhibits significant differential expression during the morphogenesis of secondary hair follicles. Our results indicate that lncRNA MRPS28 is a non-coding RNA transcribed from the intron region of the MRPS28 gene. Additionally, it can inhibit the proliferation and migration of dermal fibroblasts while promoting their apoptosis. Further mechanistic studies have shown that lncRNA MRPS28 acts as a competing endogenous RNA, sponging chi-miR-145-5p, thereby relieving its inhibitory effect on the target gene NUAK1. This, in turn, inhibits the formation of dermal papilla structures and ultimately affects the morphogenesis of secondary hair follicles during the embryonic period. This study provides a novel perspective on dissecting the regulatory network of hair follicle development in cashmere goats and offers potential theoretical insights for breeding new strains of cashmere goats.

Objective: Dermal papilla is developed from the continuous proliferation and differentiation of dermal fibroblasts, which is the key to the normal development of hair follicles. This study aims to elucidate the role of lncRNA ST6GALNAC3, which is significantly differentially expressed during the secondary hair follicle development stage in cashmere goats, on dermal fibroblasts, and to analyze the regulatory mechanism of this lncRNA thoroughly.Methods: We conducted a screening process and characterization for lncRNAs associated with the development of secondary hair follicles. The effects of lncRNA ST6GALNAC3 on cell proliferation and migration were assessed using CCK8, EdU, and flow cytometry. Subsequently, we employed bioinformatics analysis to identify the target miRNAs of lncRNA ST6GALNAC3 and the corresponding target genes of these miRNAs, respectively, and initially constructed the regulatory axis of lncRNA ST6GALNAC3-chi-miR-24-3p-ID4. Luciferase reporter assays and rescue experiments were performed to confirm the regulatory axis at both molecular and cellular levels, thus elucidating the mechanism by which lncRNA ST6GALNAC3 regulates dermal fibroblasts.Results: One hundred fifty-eight lncRNAs related to secondary hair follicle morphogenesis were identified. Among them, lncRNA ST6GALNAC3 was significantly differentially expressed on embryonic day 75 and significantly inhibited the proliferation and migration of dermal fibroblasts. The results showed that lncRNA ST6GALNAC3 can target chi-miR-24-3p, which in turn can target the ID4 gene. The results of the luciferase reporter assay and rescue assay showed that chi-miR-24-3p binds to both lncRNA ST6GALNAC3 and ID4. Furthermore, lncRNA ST6GALNAC3 can indirectly regulate the proliferation and migration of dermal fibroblasts through chi-miR-24-3p/ID4 axis.Conclusion: LncRNA ST6GALNAC3 inhibits the proliferation and migration of dermal fibroblasts through the chi-miR-24-3p/ID4 axis, thus suppressing the formation of dermal papilla structures and influencing the morphogenesis of secondary hair follicles during embryonic development.