miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.
Lingfang WangXing DuQiqi LiWangjun WuZengxiang PanQifa LiPublished in: Cell death discovery (2021)
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.
Keyphrases
- transforming growth factor
- cell proliferation
- epithelial mesenchymal transition
- long non coding rna
- signaling pathway
- long noncoding rna
- cell cycle arrest
- induced apoptosis
- pi k akt
- copy number
- oxidative stress
- endoplasmic reticulum stress
- cell death
- transcription factor
- type diabetes
- skeletal muscle
- metabolic syndrome
- polycystic ovary syndrome
- young adults
- genome wide