DCN promotes dermal papilla cells proliferation by escaping chi-miR-497-5p mediated repression via circPIEZO2...

The proliferation and apoptosis of dermal papilla cells (DPCs) are crucial for hair follicle morphogenesis and development. High-throughput sequencing data revealed that decorin (DCN) is significantly highly expressed during the organogenesis phase of cashmere goat hair follicles, primarily within dermal lineage cells. However, its specific function and regulatory mechanisms in hair follicle morphogenesis and development remain unclear. This study focused on the role of DCN in DPCs, and functional experiments showed that DCN overexpression significantly promoted DPCs proliferation and inhibited DPCs apoptosis. Further transcriptome analysis identified a circRNA, named as circPIEZO2, which was positively expressed with DCN. Functional validation revealed that the inhibition of circPIEZO2 suppressed DPCs proliferation and induced DPCs apoptosis. Mechanistic studies revealed that circPIEZO2 was primarily localized in the cytoplasm, where it acted as a molecular sponge for chi-miR-497-5p. By sequestering chi-miR-497-5p, circPIEZO2 alleviated the inhibitory effect of chi-miR-497-5p on the binding to the 3'UTR of the DCN gene, ultimately upregulating DCN expression. Importantly, the overexpression of either DCN or circPIEZO2 activated the Wnt/β-catenin signaling pathway and upregulated its downstream proliferation-related genes Cyclin D1 and C-myc. Conversely, the overexpression of chi-miR-497-5p suppressed the activity of this pathway. In conclusion, this study elucidates the core role of the circPIEZO2/chi-miR-497-5p/DCN regulatory axis in regulating DPCs proliferation and apoptosis. These findings provide novel potential targets and a theoretical basis for cashmere goat breeding and therapeutic targets for hair loss.