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MiR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.

ABSTRACT: Transforming growth factor-β1 (TGF-β1) is essential for ovarian function and female fertility in mammals. Herein, we identified three completely linked variants, including two known variants referred to as c.1583A > G and c.1587A > G and the novel variant c.2074A > C in the porcine TGF-β1 3'-UTR. An important role of these variants in Yorkshire sow fertility was revealed. Variants c.1583A > G and c.1587A > G were located at the miRNA response element (MRE) of miR-2337 and affected miR-2337 regulation of TGF-β1 3'-UTR activity. Interestingly, miR-2337 induces, not reduces the transcription and production of TGF-β1 in granulosa cells (GCs). Mechanistically, miR-2337 enhances TGF-β1 promoter activity via the MRE motif in the core promoter region and alters histone modifications, including H3K4me2, H3K4me3, H3K9me2, and H3K9ac. In addition, miR-2337 controls TGF-β1-mediated activity of the TGF-β signaling pathway and GC apoptosis. Taken together, our findings identify miR-2337 as an endogenous small activating RNA (saRNA) of TGF-β1 in GCs, while miR-2337 is identified as a small activator of the TGF-β signaling pathway which is expected to be a new target for rescuing GC apoptosis and treating low fertility.

SUBMITTER: Wang L

PROVIDER: S-EPMC8449777 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339.

Project description:BackgroundFunctioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus.ResultsWe identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis.ConclusionsOur findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.

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LPS induces HUVEC angiogenesis <i>in vitro</i> through miR-146a-mediated TGF-β1 inhibition.

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TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome.

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TGF-β1 induces bone marrow NK cells dysfunction

Project description:TGF-β1 is a cytokine of the bone morphogenetic protein–activin family and commonly regarded as the most powerful immunosuppressive cytokine

2023-11-22 | GSE190546 | GEO

The role of TGF-β1-miR-21-ROS pathway in bystander responses induced by irradiated non-small-cell lung cancer cells.

Project description:Many studies have indicated an important implication of radiation-induced bystander effects (RIBEs) in cancer radiotherapy, but the detailed signalling remains unclear.The roles of tumour growth factor-beta1 (TGF-β1) and miR-21 in medium-mediated RIBEs in H1299 non-small-cell lung cancer cells were investigated using DNA damage, changes in proliferation and levels of reactive oxygen species (ROS) as end points. SB431542, a specific inhibitor of TGF-β type 1 receptor kinases, was used to inhibit TGF-β1 pathways in irradiated and bystander cells. Exogenous miR-21 regulation was achieved through inhibitor or mimic transfection.Compared with relative sham-radiation-conditioned medium, radiation-conditioned medium (RCM) from irradiated cells 1 h post radiation (1-h RCM) caused an increase in ROS levels and DNA damage in bystander cells, while 18-h RCM induced cell cycle delay and proliferation inhibition. All these effects were eliminated by TGF-βR1 inhibition. One-hour RCM upregulated miR-21 expression in bystander cells, and miR-21 inhibitor abolished bystander oxidative stress and DNA damage. Eighteen-hour RCM downregulated miR-21 of bystander cells, and miR-21 mimic eliminated bystander proliferation inhibition. Furthermore, the dysregulation of miR-21 was attenuated by TGF-βR1 inhibition.The TGF-β1-miR-21-ROS pathway of bystander cells has an important mediating role in RIBEs in H1299 cells.

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Decitabine reverses TGF-β1-induced epithelial-mesenchymal transition in non-small-cell lung cancer by regulating miR-200/ZEB axis.

Project description:ObjectiveEpithelial-mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-β1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment.MethodsIn this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-β1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis.ResultsDecitabine reversed TGF-β1-induced EMT in PC9 cells, but not in A549 cells. This phenomenon was associated with epigenetic changes in the miR-200 family, which regulated EMT by altering the expression of ZEB1 and ZEB2. TGF-β1 induced aberrant methylation in miR-200 promoters, leading to EMT in PC9 cells. Decitabine attenuated this effect and inhibited tumor cell migration in vitro and in vivo. In A549 cells, however, neither TGF-β1 nor decitabine exhibited an effect on miR-200 promoter methylation.ConclusionOur findings suggest that epigenetic regulation of the miR-200/ZEB axis is responsible for EMT induction by TGF-β1 in PC9 cells. Decitabine inhibits EMT in NSCLC cell PC9 through its epigenetic-based therapeutic activity.

| S-EPMC5378468 | biostudies-literature

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1.

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| S-EPMC8238984 | biostudies-literature

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