miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells

oleh: Liu Yang, Xing Du, Lu Liu, Qiuyu Cao, Zengxiang Pan, Qifa Li

Format: Article
Diterbitkan: MDPI AG 2019-03-01

Deskripsi

Transforming growth factor-&#946; receptor II (TGFBR2), the type II receptor of the TGF-&#946;/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-&#946; signal transduction and is regulated by multiple factors. Nevertheless, the modulation of the non-coding RNA involved in the process of <i>TGFBR2</i> expression in ovaries is not well studied. In our study, we isolated and characterized the 3&#8242;-untranslated region (UTR) of the porcine <i>TGFBR2</i> gene and microRNA-1306 (miR-1306) was identified as the functional miRNA that targets TGFBR2 in porcine granulosa cells (GCs). Functional analysis showed that miR-1306 promotes apoptosis of GCs as well as attenuating the TGF-&#946;/SMAD signaling pathway targeting and impairing TGFBR2 in GCs. Moreover, we identified the miR-1306 core promoter and found three potential SMAD4-binding elements (SBEs). Luciferase and chromatin immunoprecipitation (ChIP) assays revealed that the transcription factor SMAD4 directly binds to the miR-1306 core promoter and inhibits its transcriptional activity. Furthermore, the TGF-&#946;/SMAD signaling pathway is modulated by SMAD4 positive feedback via inhibition of miR-1306 expression in GCs. Collectively, our findings provide evidence of an epigenetic mechanism that modulates as well as mediates the feedback regulation of the classical TGF-&#946;/SMAD signaling pathway in GCs from porcine ovaries.