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

ABSTRACT: 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 8,721 differentially expressed circRNAs (DECs), 143 differentially expressed miRNAs (DEMs) and 2,238 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.

ORGANISM(S): Ovis aries

PROVIDER: GSE288804 | GEO | 2025/03/26

REPOSITORIES: GEO

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Project description:Effective management and control of parasitic infections on farms depends on their early detection. Traditional serological diagnostic methods for Fasciola hepatica infection in livestock are specific and sensitive, but currently the earliest detection of the parasite only occurs at approximately three weeks post-infection. At this timepoint, parasites have already entered the liver and caused the tissue damage and immunopathology that results in reduced body weight and loss in productivity. Here, we investigated whether the differential abundance of micro(mi)miRNAs in sera of F. hepatica-infected sheep has potential as a tool for the early diagnosis of infection. Using miRNA sequencing analysis, we discovered specific profiles of sheep miRNAs at both the pre-hepatic and hepatic infection phases in comparison to non-infected sheep. In addition, six F. hepatica-derived miRNAs were specifically identified in sera from infected sheep. Thus, a panel of differentially expressed miRNAs comprising four sheep (miR-3231-3p; miR133-5p; 3957-5p; 1197-3p) and two parasite miRNAs (miR-124-3p; miR-Novel-11-5p) were selected as potential biomarkers. The expression of these candidates in sera samples from longitudinal sheep infection studies collected between 7 days and 23 weeks was quantified using RT-qPCR and compared to samples from age-matched non-infected sheep. We identified oar-miR-133-5p and oar-miR-3957-5p as promising biomarkers of fasciolosis, detecting infection as early as 7 days. The differential expression of the other selected miRNAs was not sufficient to diagnose infection; however, our analysis found that the most abundant forms of fhe-miR-124-3p in sera were sequence variants (IsomiRs) of the canonical miRNA, highlighting the critical importance of primer design for accurate diagnostic RT-qPCR. Accordingly, this investigative study suggests that certain miRNAs are biomarkers of F. hepatica infection and validates miRNA-based diagnostics for the detection of fasciolosis in sheep.

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

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