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miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway

Lei Yang1,2, Qizhuang Lv3,4, Jianyun Liu1,2

  • 1Key Laboratory of System Bio-medicine of Jiangxi Province, Jiujiang University, Jiangxi 332000, PR China.

The Journal of Reproduction and Development
|February 14, 2020
PubMed

Insights

MicroRNA-431 (miR-431) regulates ovarian granulosa cell function by targeting Insulin receptor substrate 2 (IRS2). This interaction impacts the PI3K/AKT pathway, affecting cell proliferation and hormone synthesis during ovarian development.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cell Signaling

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression, influencing cellular functions.
  • Insulin receptor substrate 2 (IRS2) is implicated in ovarian hormone regulation, but its interaction with specific miRNAs like miR-431 is underexplored.
  • The role of miR-431 and its signaling pathway in ovarian development requires elucidation.

Purpose of the Study:

  • To investigate the expression patterns of miR-431 and IRS2 during the estrous cycle and ovarian development.
  • To determine the function and signaling pathway of miR-431 in human granulosa cells (COV434).
  • To confirm IRS2 as a direct target of miR-431.

Main Methods:

  • Analysis of miR-431 and IRS2 expression following pregnant mare serum gonadotropin (PMSG) stimulation.
  • Functional studies in COV434 cells involving miR-431 overexpression and IRS2 knockdown.
  • Luciferase reporter assays to validate miRNA-target interaction.
  • Assessment of AKT activation, cell proliferation, and steroid hormone synthesis (estradiol and progesterone).

Main Results:

  • Follicle stimulating hormone (FSH) decreased miR-431, increased IRS2, and promoted pAKT expression.
  • miR-431 overexpression and IRS2 knockdown reduced AKT activation, cell proliferation, and estradiol/progesterone synthesis.
  • IRS2 was confirmed as a direct target of miR-431.

Conclusions:

  • miR-431 negatively regulates granulosa cell function by targeting IRS2.
  • The miR-431/IRS2 axis modulates the PI3K/AKT signaling pathway.
  • This pathway is critical for regulating granulosa cell proliferation and steroidogenesis during ovarian development.
Keywords:
Cell proliferationEstradiolGranulosa cellsInsulin receptor substrate 2miR-431

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