MiR ‐376c‐3p Targets STRBP mRNA to Regulate Cashmere Goat Hair Follicle Stem Cell Proliferation

ABSTRACT

The quality of cashmere fiber is fundamentally determined by the embryonic morphogenesis of hair follicles, a process highly dependent on the normal function of hair follicle stem cells (HFSCs). MicroRNAs (miRNAs) are key post‐transcriptional regulators, but their specific roles in cashmere goat hair follicle development remain unclear. In this study, we identified the differentially expressed miRNA, miR‐376c‐3p, by analyzing transcriptomic data from embryonic skin (E65, E90, E120) of cashmere goats. Functional assays, including CCK8, crystal violet staining, clonogenic assay, and analysis of proliferation/apoptosis‐related proteins (PCNA, CDK4, MKI67, BCL2, CAS3 and CAS9), demonstrated that miR‐376c‐3p significantly inhibited HFSCs proliferation, induced apoptosis, and blocked the differentiation process, as evidenced by the downregulation of differentiation‐associated keratins (KRT4, KRT10, KRT14) and the upregulation of stemness maintenance factors (OCT4, NANOG, SOX9 and KRT15). Mechanistic investigations revealed that miR‐376c‐3p directly bound to the 3′UTR of STRBP mRNA and inhibited its expression, which was validated by a dual‐luciferase reporter assay. Conversely, overexpression of STRBP promoted HFSCs proliferation and differentiation. Further analysis found that STRBP functioned by activating the Wnt/β‐catenin and BMP signaling pathways, whereas miR‐376c‐3p inhibited these same pathways. In summary, this study elucidates a novel regulatory axis: miR‐376c‐3p influencing the Wnt/β‐catenin and BMP signaling cascades in HFSCs by targeting STRBP mRNA, thereby regulating cell fate. This research provides important insights into the molecular mechanisms of miRNA‐mediated hair follicle morphogenesis and stem cell biology in cashmere goats.