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MiR-1306 Mediates the Feedback Regulation of the TGF-?/SMAD Signaling Pathway in Granulosa Cells.


ABSTRACT: Transforming growth factor-? receptor II (TGFBR2), the type II receptor of the TGF-?/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-? signal transduction and is regulated by multiple factors. Nevertheless, the modulation of the non-coding RNA involved in the process of TGFBR2 expression in ovaries is not well studied. In our study, we isolated and characterized the 3'-untranslated region (UTR) of the porcine TGFBR2 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-?/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-?/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-?/SMAD signaling pathway in GCs from porcine ovaries.

SUBMITTER: Yang L 

PROVIDER: S-EPMC6523565 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Yang Liu L   Du Xing X   Liu Lu L   Cao Qiuyu Q   Pan Zengxiang Z   Li Qifa Q  

Cells 20190331 4


Transforming growth factor-β receptor II (TGFBR2), the type II receptor of the TGF-β/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-β 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'-untranslated region (UTR) of the porcine <i>TGFBR2</i> gene and microRNA-1306 (miR-130  ...[more]

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