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MiR-126* is a novel functional target of transcription factor SMAD4 in ovarian granulosa cells

Qiqi Li1, Xing Du1, Lu Liu1

  • 1College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

Gene
|July 4, 2019
PubMed

Insights

SMAD4 acts as a transcription factor to suppress miR-126* expression in porcine granulosa cells (GCs). This regulation impacts the miR-126*/FSHR axis, influencing GC apoptosis and function.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cellular Signaling

Background:

  • SMAD4 and miR-126* are implicated in granulosa cell (GC) apoptosis and follicular atresia.
  • Both factors commonly regulate the follicle-stimulating hormone receptor (FSHR) in GCs.
  • The precise regulatory relationship between SMAD4 and miR-126* in GCs remains unclear.

Purpose of the Study:

  • To elucidate the regulatory relationship between SMAD4 and miR-126* in porcine ovarian GCs.
  • To investigate the mechanism by which SMAD4 influences miR-126* expression and function.
  • To understand the role of the SMAD4-miR-126*-FSHR axis in GC apoptosis and function.

Main Methods:

  • In silico analysis to identify SMAD4-binding elements (SBE) in the miR-126* promoter.
  • Luciferase assays to confirm transcriptional activity.
  • Quantitative reverse transcription PCR (qRT-PCR) to measure gene expression.
  • Chromatin immunoprecipitation (ChIP) assays to assess protein-DNA binding.

Main Results:

  • SMAD4 directly binds to the SBE site in the miR-126* promoter, acting as a transcriptional repressor.
  • SMAD4 significantly reduces miR-126* gene expression and its transcriptional activity in GCs.
  • SMAD4 regulates FSHR expression mediated by miR-126* and induces CYP19A1 expression, inhibiting GC apoptosis via the miR-126*/FSHR axis.

Conclusions:

  • SMAD4 directly suppresses miR-126* expression in porcine GCs by binding to its promoter.
  • The study establishes a novel regulatory link between SMAD4 and miR-126*, impacting GC apoptosis.
  • The findings reveal the miR-126*/FSHR axis as a key pathway through which SMAD4 regulates GC function and survival.
Keywords:
Granulosa cell apoptosisPigSMAD4miR-126*

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