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

Estrogen is an important hormone affecting muscle development in female animals. Studies have shown that estrogen can protect muscle cells from apoptosis by inhibiting MAPK signaling pathway. However, the molecular mechanisms by which estrogen-induced MAPK signaling regulates myoblasts growth and development remain unclear. In this study, RNA-seq was performed in the ovariectomized small-tailed Han (OR-STH) sheep and sham surgery small-tailed Han (STH) sheep groups to analyze the effect of estrogen on muscle growth and development in female animals. There were identified 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 showed 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 molecular mechanism experiments indicated that circFAM171A1 could act as a sponge adsorbing oar-miR-485-5p to regulate MAPK15 . Addition of the exogenous hormone estradiol (E ₂ ) 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 proliferation of myoblasts and inhibited apoptosis of myoblasts in sheep, whereas oar-miR-485-5p inhibited expression of MAPK15 and circFAM171A1 and inhibited myoblast proliferation and promoted apoptosis. Furthermore, circFAM171A1 could attenuate 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 finally regulated the proliferation of sheep myoblasts. This study provided new insights for molecular mechanism of estrogen regulation on muscle growth and development in female animals.