Aug 2026· International Journal of Molecular Sciences· Vol 27· 0 citations· 45 references
Medicine
TL;DR
The 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.
Abstract
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.
A bta-miR-380-3p-SOAT1 regulatory axis linking post-transcriptional control with cholesterol metabolism, preadipocyte expansion, and IMF deposition is revealed, providing mechanistic insight and a potential molecular target for improving marbling and meat quality traits in cattle breeding programs.
Diba Dedacha Jilo, B. Abebe, Jun-Tao Guo et al.· International Journal of Bio...· 0 citations
MicroRNAs (miRNAs) play critical roles in regulating follicular development and atresia by modulating autophagy, apoptosis, and steroidogenesis in granulosa cells (GCs). However, the role of specific miRNAs in these processes remains poorly understood. In this study, we focused on miR-6615-3p to explore its function and molecular mechanism in chicken Prehierarchical follicular granulosa cells (PFGCs). The expression of miR-6615-3p in chicken PFGCs was confirmed by qRT-PCR. Dual-luciferase reporter assays identified the androgen receptor (AR) gene as a direct target of miR-6615-3p. Functional analyses revealed that miR-6615-3p suppressed AR expression, promoted apoptosis, and inhibited both autophagy and steroidogenesis in PFGCs. Together, these results suggest that miR-6615-3p downregulates AR and is associated with reduced MDM2 expression, enhanced p53 activation, and decreased BCL2 expression. This indicates that it may regulate cell fate and steroid hormone synthesis, at least in part, through the MDM2-p53-BCL2 signaling pathway. This study provides new insights into the molecular mechanisms underlying chicken follicular development and highlights miR-6615-3p as a potential molecular marker for improving reproductive performance in poultry.
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.
Gaoqing Xu, Chunqi Hou, He Ding et al.· Animal Genetics· 0 citations
MicroRNAs are important post-transcriptional regulators of intracellular signaling pathways that govern cell proliferation, apoptosis, and cell-cycle progression. However, whether miR-424-3p regulates PIP5K1C-associated AKT signaling in granulosa cells remains unclear. In this study, we investigated the molecular mechanism of miR-424-3p in goat granulosa cells (GCs). RT-qPCR analysis showed that miR-424-3p was more highly expressed in large follicles than in small follicles. Gain- and loss-of-function assays revealed that miR-424-3p inhibited GC proliferation, reduced the proportion of cells in S phase, and promoted apoptosis. Western blot analysis showed that miR-424-3p decreased the protein levels of CDK6 and CCND1. Dual-luciferase reporter assays and Western blotting identified BCL2 and PIP5K1C as direct targets of miR-424-3p. Functional rescue experiments further demonstrated that PIP5K1C overexpression promoted GC proliferation, increased CCND1 expression, and partially counteracted the inhibitory effects of miR-424-3p. Mechanistically, miR-424-3p suppressed AKT phosphorylation, whereas PIP5K1C enhanced AKT phosphorylation, suggesting that the miR-424-3p/PIP5K1C axis regulates GC fate through AKT signaling. These findings identify a previously unrecognized miR-424-3p/PIP5K1C/AKT regulatory axis that links post-transcriptional gene regulation to AKT-dependent granulosa cell proliferation and apoptosis.
AIM: To investigate the functions of microRNA-26a-5p (miR-26a-5p) in the high glucose (HG)-induced rat retinal Müller cells (rMC-1) apoptosis and its possible mechanism.
METHODS: rMC-1 cells were transfected with miR-26a-5p mimics or phosphatase and tensin homolog (PTEN) siRNA under HG conditions. Cell apoptosis was analyzed by propidium iodide (PI) and annexin V fluorescein isothiocyanate (FITC) staining. PTEN/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway activation was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Inflammatory cytokines, interleukin (IL)-1β, IL-6, were measured by enzyme-linked immunosorbent assay (ELISA). The miR-26a-5p-PTEN interaction was validated by dual-luciferase assay.
RESULTS: HG significantly suppressed miR-26a-5p expression and induced apoptosis in rMC-1 cells. Overexpression of miR-26a-5p attenuated HG-induced apoptosis by directly targeting PTEN, as confirmed by dual-luciferase reporter assay, which demonstrated that miR-26a-5p directly binds to the PTEN 3’-UTR, resulting in a 50% reduction in luciferase activity (P<0.01). Consistent with this, miR-26a-5p overexpression downregulated PTEN expression, enhanced PI3K/Akt phosphorylation, and suppressed the secretion of IL-1β and IL-6 (all P<0.01).
CONCLUSION: Upregulation of miR-26a-5p protects rMC-1 from HG-induced apoptosis by targeting PTEN via regulating the PI3K/Akt pathway and inflammatory responses. miR-26a-5p may be a potential therapeutic target for diabetic retinal neurodegeneration.
Rui Shi, De-Rong Tang, Di Li et al.· International Journal of Oph...· 0 citations
It is indicated that SLC12A9-AS1 is abnormally overexpressed in CRC cells and that its knockdown attenuates malignant phenotypes, at least in part through regulation of miR-139-3p.
Shiyu Zhao, Shuai Zhang, Qiongfeng Tan et al.· Journal of Visualized Experi...· 0 citations
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