Aug 2026· Animal Genetics· Vol 57 4, pp.
e70172
· 0 citations· 43 references
Medicine
TL;DR
Findings reveal a novel epigenetic regulatory axis (novel-miR-357/S100A2 mRNA) involved in early muscle development and provide an important molecular mechanism for deeper understanding of the epigenetic regulatory processes underlying heterosis in cattle.
Abstract
The unresolved mechanisms underlying heterosis in beef cattle production traits hinder the optimization of crossbreeding strategies. In this study, we generated Wagyu × Hereford hybrid cattle (F1) and observed significantly enhanced growth rates compared to purebred Hereford controls, prompting further investigation into the epigenetic regulatory basis of heterosis in bovine muscle development. Combined microRNA-seq and RNA-seq profiling of the longissimus dorsi muscle identified 17 differentially expressed miRNAs and 489 differentially expressed genes (DEGs), enabling the construction of a comprehensive miRNA-mRNA regulatory network. Notably, decreased expression of bta-novel-miR-357 (novel-miR-357) and increased expression of S100A2 (S100 Calcium-Binding Protein A2) mRNA were observed in the hybrid cattle. Functional assays in primary bovine myoblasts demonstrated that novel-miR-357 and siS100A2 inhibited cell proliferation and promoted apoptosis. Dual-luciferase reporter assays confirmed that novel-miR-357 directly binds to the 3'UTR of S100A2 mRNA, establishing a targeted regulatory relationship. Furthermore, novel-miR-357 was shown to inhibit proliferation and promote apoptosis of bovine myoblasts through targeting S100A2 mRNA. These findings reveal a novel epigenetic regulatory axis (novel-miR-357/S100A2 mRNA) involved in early muscle development and provide an important molecular mechanism for deeper understanding of the epigenetic regulatory processes underlying heterosis in cattle. Nevertheless, given the polygenic complexity of heterosis, it is important to recognize that this pathway likely represents only one of several contributing factors to this complex trait.
Adipose tissue development significantly influences meat quality and economic traits in beef cattle. In this study, we identified a novel circular RNA derived from two exons (exons 3 and exons 9) of the NID2 gene, designated as circNID2, which exhibits high structural stability and marked upregulation during bovine adipocyte differentiation. Functional assays demonstrated that circNID2 suppresses the proliferation and apoptosis of bovine preadipocytes while robustly promoting adipogenic differentiation and lipid accumulation. Although containing several putative open reading frames, circNID2 lacks protein-coding potential. Mechanistically, circNID2 functions as a competing endogenous RNA by sponging miR-339a, thereby relieving the post-transcriptional repression of its downstream target, Neuronatin (NNAT). Functional rescue experiments further validated that circNID2 partially neutralizes the regulatory effects of miR-339a on preadipocyte proliferation, apoptosis, and differentiation. Collectively, these findings demonstrate that circNID2 regulates bovine preadipocyte function through the newly established circNID2/miR-339a/NNAT axis. This study provides novel insights into the post-transcriptional mechanisms governing mammalian adipogenesis and highlights circNID2 as a potential molecular target for improving fat deposition traits in cattle.
Yue Liu, Mengyang Zhang, Zhuoyuan He et al.· Biomolecules· 0 citations
Intramuscular fat (IMF) deposition significantly impacts beef quality, yet microRNA (miRNA)-mediated mechanisms regulating bovine intramuscular preadipocyte development are not fully understood. This study aimed to elucidate the role of bta-miR-380-3p in preadipocyte proliferation, apoptosis, and adipogenic differentiation, identifying sterol O-acyltransferase 1 (SOAT1) as its functional target. Bta-miR-380-3p exhibited dynamic expression during adipogenesis and was highly expressed in adult bovine IMF. Gain- and loss-of-function assays showed that bta-miR-380-3p promoted DNA synthesis, cell viability, and cell-cycle progression, and reduced apoptosis-related signaling. Consistently, western blot analysis confirmed increased PCNA and CDK1 and reduced P21 after bta-miR-380-3p overexpression, whereas inhibition produced the opposite pattern. Bta-miR-380-3p also enhanced lipid droplet accumulation and upregulated adipogenic markers, with western blotting confirming increased PPARγ, FABP4, and SREBP1 protein abundance. Bioinformatics prediction, expression validation, and dual-luciferase reporter assays demonstrated that bta-miR-380-3p directly targets the SOAT1 3'UTR and negatively regulates SOAT1 expression. Functional manipulation of SOAT1 further revealed its involvement in triglyceride accumulation, adipogenic marker regulation, and proliferation-associated remodeling. Collectively, these findings reveal a bta-miR-380-3p-SOAT1 regulatory axis linking post-transcriptional control with cholesterol metabolism, preadipocyte expansion, and IMF deposition. These results provide mechanistic insight and a potential molecular target for improving marbling and meat quality traits in cattle breeding programs.
Diba Dedacha Jilo, B. Abebe, Juntao Guo et al.· International Journal of Bio...· 0 citations
Sertoli cells (SCs) are essential for spermatogenesis and provide structural and nutritional support to germ cells in the Chinese Holstein cattle testis. Although microRNAs (miRNAs) are known to regulate SC function, the specific role of Bta-miR-146a in bovine SCs is unclear. This study investigated the mechanisms by which Bta-miR-146a regulates bovine immature SCs. Using molecular cloning, we constructed Bta-miR-146a overexpression and interference vectors and transfected them into SCs via lipofection. Quantitative real-time PCR (RT-qPCR), 5-ethynyl-2′-deoxyuridine (EdU) proliferation assays, Cell Counting Kit-8 (CCK-8) viability assays, and flow cytometry revealed that Bta-miR-146a overexpression inhibited SC proliferation and promoted apoptosis, whereas Bta-miR-146a inhibition increased proliferation and suppressed apoptosis. Dual-luciferase reporter assays confirmed that SMAD4 is a direct target of Bta-miR-146a; SMAD4 interference reduced SC proliferation and increased apoptosis, whereas overexpression had the opposite effect. Furthermore, activity of this gene modulates the TGFβ/MAPK signaling pathway; SMAD4 interference reduces the expression of TGFβ, TGF-βRII, DAXX, MAP3K5, P38, and MAX. These findings indicate that the Bta-miR-146a/SMAD4/TGFβ/MAPK axis is a key regulator of SC proliferation and apoptosis, offering insights into the molecular mechanisms underlying bovine spermatogenesis and potential targets for improving reproductive performance.
Qiwen Lu, Quan-Heng Guo, Yanlong Zhou et al.· International Journal of Mol...· 0 citations
Litter size is an economically important trait in sheep and is closely associated with ovarian follicular development and granulosa cell (GC) function. This study investigated the association between GDF9 polymorphisms and litter size, and examined the post-transcriptional regulation of GDF9 by miR-6388 in ovine GCs. Variants were initially identified by Sanger sequencing in 20 ewes, and subsequently genotyped in 377 three-year-old ewes, including 231 Sonid (SN) sheep and 146 Ujimqin (UM) sheep for association analysis. Candidate miRNAs targeting litter size-associated variants in the GDF9 3'UTR were predicted, and the miR-6388-GDF9 interaction was evaluated using dual-luciferase reporter assays. RT-qPCR, Western blotting, EdU incorporation, and flow cytometry were used to assess endogenous GDF9 expression and GC function. Twelve single-nucleotide polymorphisms were identified, including the putatively novel variant g.42114076C > G. The linkage disequilibrium block comprising g.42116936C > T, g.42113821T > A, and g.42113962G > A polymorphisms of GDF9 was significantly associated with litter size in both SN and UM sheep, whereas the c.477G > A was associated with litter size only in UM sheep. Reporter assays showed that the GDF9 3'UTR region carrying the G allele of g.42113962G > A was more responsive to miR-6388-mediated repression than the region carrying the A allele. miR-6388 overexpression reduced GDF9 mRNA and GDF9 protein levels, inhibited GC proliferation, altered cell-cycle distribution, and promoted apoptosis, whereas miR-6388 knockdown increased GDF9 expression and GC proliferation and reduced apoptosis. These cellular changes were accompanied by altered expression of cell-cycle and apoptosis-related genes and TGF-β signaling-related components.
Jianyu Xu, Yanyu Bai, Xinyue An et al.· Theriogenology· 0 citations
Loss-of-function analysis of ZFC3H1 and DYNLT3 in A375 melanoma cells provides new insight into their potential roles in tumor cell growth and regulation, which may help define RNA-processing and transport mechanisms that support melanoma progression and identify novel targets for therapeutic intervention.
Roberto Aguilar, Aanvee Chawda, Elle Swoope· Journal of Immunology· 0 citations
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