Hair is the dominant feature of mammals and has a wide range of functions, including thermoregulation, body protection, sensory activity, and social interaction (Schneider et al., 2009), and is currently a research focus. After a long period of natural and artificial selection, the Inner Mongolia cashmere goat has formed an outstanding local cashmere goat breed. Its cashmere is delicate and soft and is known as a "fiber gem" (Zhang et al., 2006). The hair follicle is an important organ in cashmere goats. For Inner Mongolia cashmere goats, which mainly produce cashmere, the hair follicle development directly affects the cashmere yield and quality of the goats. Therefore, a deeper understanding of the molecular mechanism of hair follicle development is important for skin diseases and the molecular breeding of cashmere goats. Hair follicle development is a complex process involving multiple genes and non-coding RNAs (ncRNAs), but the specific mechanism remains to be explored.

MicroRNAs (miRNAs) are a class of endogenous ncRNAs that inhibit the expression of downstream target genes through post-transcriptional regulation. There is growing evidence that miRNAs regulate a variety of biological processes, including skin cell proliferation, migration, and apoptosis. For example, chi-miR-370–3p inhibits the proliferation of epithelial cells and dermal fibroblasts through targeted regulation of FGFR2 and TGF-βR2, thereby promoting their migration ability without affecting the apoptosis process (Hai et al., 2021). Chi-miR130b-3p targeting WNT10A promotes the proliferation of epithelial cells and dermal fibroblasts (Wu et al., 2021b). MiR-22–5p targeting binds LEF1 to inhibit proliferation of hair follicle stem cells (Yan et al., 2019). Exosome miR-181a-5p activates the Wnt/β-catenin signaling pathway by targeting the Wnt inhibitor WIF1, promoting the proliferation of hair follicle stem cells and inhibiting the apoptosis process of hair follicle stem cells (Zhao et al., 2022). MiR-181b-5p inhibits the proliferation of human epidermal keratinocytes by targeting Akt3(Zheng et al., 2019). However, the targeting relationship between miR-181b-5p and TNFSF11 in cashmere goat embryonic fibroblasts has received little attention.

Circular RNAs (circRNAs) are closed circular RNA transcripts formed by the reverse splicing of a single RNA precursor. It is found in all higher eukaryotes, including mammals (Nigro et al., 1991). The most prominent feature of circRNAs is their closed circular structure. It avoids degradation by RNase (Jeck et al., 2013) and is more conducive to its biological function. There is increasing evidence that circRNAs located in the cytoplasm can bind miRNAs as competing endogenous RNAs (ceRNAs) and thus participate in a variety of physiological processes. CircCOL1A1 reduces inhibition of CMTM3 by targeting miR-149–5p, thereby further controlling the CMTM3/AR axis. CircCOL1A1 knockdown promoted the proliferation and differentiation of cultured goat hair follicle stem cells in vitro and inhibited the apoptosis of stem cells. Overexpression of circCOL1A1 showed the opposite effect (Wang et al., 2022). CircAGK promotes apoptosis of dermal papilla cells by targeting miR-3180–5p/BAX axis and inhibits hair growth in androgen-treated mice (Wei et al., 2023). CircRNA-1926 acts as a sponge of miR-148a/b-3p to promote the expression of CDK19 gene and the differentiation of secondary hair follicle stem cells into the hair follicle lineages of cashmere goats (Yin et al., 2020). CircRNA-1967 targets miR-1–93p to up-regulate LEF3 expression and can also enhance LEF1 expression by sponging miR-93–3p to promote the differentiation of goat hair follicle stem cells (Zhu et al., 2023). This is despite the fact that circRNA plays an important role in hair follicle stem cells. However, hair follicle development is a multi-cellular process in which fibroblasts play an important role, and further studies are needed to verify the functional mechanism of circRNAs in fibroblasts.

In our previous study, we identified 113 differences associated with secondary hair follicle morphogenesis and the development circRNA (Shang et al., 2022a). CircERBB3, named after the erb-b2 receptor tyrosine kinase 3 (ERBB3) gene, is formed by cyclization of exons 13, 14, 15, 16, 17, and 18 of ERBB3. ERBB3 is essential to the development and homeostasis of the epidermis and its appendages. ERBB3 can promote wound healing and skin tumor progression when the body is stimulated by injury or carcinogenesis (Dahlhoff et al., 2015). In human keratinocyte lines, ERBB3 deficiency inhibits apoptosis. All in all, ERBB3 plays an important role in skin development. This suggests that circERBB3 has an important and potentially conservative function.

In this study, we aimed to investigate the role of circRNA in regulating the proliferation, migration, and apoptosis of skin fibroblasts. We are the first to explored the endogenous expression and function of circERBB3 in skin fibroblasts and how circERBB3 participates in proliferation, migration, and apoptosis of skin fibroblasts through sponge miRNA. We found that circERBB3 is an important regulatory factor in the proliferation, migration, and apoptosis of skin fibroblasts. Our study provides new insights into the complex RNA regulatory mechanisms of hair follicles in cashmere goats.