An anti-sense lncRNA of the A-FABP gene regulates the proliferation of hair follicle stem cells via the chi-miR-335-5p/DKK1/β-catenin axis.

Abstract

Hair follicle development relies on both the epithelial-mesenchymal interaction (EMI) and the proliferation of hair follicle stem cells (HFSCs). This intricate process involves numerous regulatory molecules. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play a crucial role in hair follicle development. However, the functions and molecular mechanisms of many lncRNAs in hair follicle development of cashmere goats remain unclear. Based on our previous lncRNA sequencing results in cashmere goats, an unannotated lncRNA differentially expressed at various stages of hair follicle development, named FABP_AS, was detected. Consequently, we aimed at exploring the function and molecular mechanisms of FABP_AS. We constructed a CRISPR/Cas9 knockout system to specifically knock down FABP_AS, providing a reference model for target lncRNA knockout in animal primary cells. Functional experiment results demonstrated that FABP_AS significantly inhibited HFSCs proliferation. Mechanism experiment results revealed that FABP_AS competitively bond to chi-miR-335-5p, promoted DKK1 gene expression, and reduced Wnt/β-catenin signaling pathway activity. In summary, our findings indicated that FABP_AS acted as a miRNA sponge, sequestering chi-miR-335-5p away from the DKK1 gene, thereby suppressing HFSCs proliferation, which would lay the groundwork for a better understanding of the molecular mechanisms of hair follicle development and provide therapeutic targets for hair loss.