Estrogen-induced circFAM171A1 regulates sheep myoblast proliferation through the oar-miR-485-5p/MAPK15/MAPK pathway

Estrogen is an important hormone that affects muscle development in female animals. Previous studies have shown that estrogen can protect muscle cells from apoptosis by inhibiting the MAPK signaling pathway. However, the molecular mechanisms by which estrogen-induced MAPK signaling regulates myoblast growth and development remain unclear. In this study, RNA-seq was performed on ovariectomized small-tailed Han (OR-STH) sheep and sham surgery small-tailed Han (STH) sheep to analyze the effects of estrogen on muscle growth and development in female animals. There were 8721 differentially expressed circRNAs (DECs), 143 differentially expressed miRNAs (DEMs) and 2238 differentially expressed mRNAs (DEGs) in the longissimus dorsi between the OR-STH and STH groups. Bioinformatics analysis revealed that the differentially expressed gene MAPK15 was significantly enriched in the MAPK signaling pathway, which is important for muscle development. Therefore, we constructed the ceRNA network circFAM171A1/oar-miR-485-5p/MAPK15 and explored its effect on muscle growth and development. The results of the molecular mechanism experiments indicated that circFAM171A1 can sponge oar-miR-485-5p to regulate MAPK15. The addition of the exogenous hormone estradiol (E₂) to sheep myoblasts could induce circFAM171A1, regulate the expression of oar-miR-485-5p and MAPK15, and promote the proliferation of sheep myoblasts. The results showed that MAPK15 and circFAM171A1 significantly promoted the proliferation of myoblasts and inhibited the apoptosis of myoblasts in sheep, whereas oar-miR-485-5p inhibited the expression of MAPK15 and circFAM171A1, inhibited myoblast proliferation and promoted apoptosis. Furthermore, circFAM171A1 attenuated the inhibitory effect of oar-miR-485-5p on myoblasts. In summary, estrogen induced the expression of circFAM171A1 in sheep myoblasts, and circFAM171A1 can act as a sponge for oar-miR-485-5p to promote the expression of the target gene MAPK15 and ultimately regulate the proliferation of sheep myoblasts. This study provides new insights into the molecular mechanism of estrogen regulation of muscle growth and development in female animals.