LncRNA ST6GALNAC3 inhibits dermal fibroblast proliferation and migration in cashmere goat hair follicles via the chi-miR-24-3p/ID4 axis

Abstract

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-miR24-3p, 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.