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miRNA-125a modulates autophagy of thyroiditis through PI3K/Akt/mTOR signaling pathway

Danyan Chen1, Xiaolong Huang1, Song Lu1

  • 1Department of Endocrinology and Nephrology, The Zhongshan District of Chongqing General Hospital, Chongqing 400231, P.R. China.

Experimental and Therapeutic Medicine
|March 26, 2019
PubMed

Insights

MicroRNA-125a (miR-125a) is upregulated in thyroiditis, inhibiting autophagy and promoting inflammation by targeting the PI3K/Akt/mTOR pathway. This suggests miR-125a plays a key role in thyroiditis pathogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Thyroiditis is an inflammatory condition affecting the thyroid gland.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases.
  • The specific role of microRNA-125a (miR-125a) in thyroiditis remains largely unexplored.

Purpose of the Study:

  • To investigate the function and mechanisms of miR-125a in a mouse model of thyroiditis.
  • To elucidate the signaling pathway involved in miR-125a-mediated effects on thyroiditis.

Main Methods:

  • Thyroiditis model established in mice via subcutaneous injection of porcine thyroglobulin.
  • In vitro studies using a mouse macrophage cell line stimulated with human interferon-γ.
  • miR-125a expression modulated using mimic transfection.
  • Analysis of autophagy, cell proliferation, apoptosis, pro-inflammatory factors, and the PI3K/Akt/mTOR signaling pathway.

Main Results:

  • Serum miR-125a expression was significantly upregulated in mice with thyroiditis.
  • In vitro, increased miR-125a expression reduced autophagy and cell proliferation.
  • miR-125a overexpression elevated apoptosis and pro-inflammatory cytokine expression (TNF-α, IL-1β, IL-6, IL-18) by downregulating the PI3K/Akt/mTOR pathway.
  • PI3K inhibition potentiated the pro-inflammatory effects of miR-125a.

Conclusions:

  • miR-125a plays a critical role in thyroiditis by inhibiting autophagy.
  • The PI3K/Akt/mTOR signaling pathway is a key mediator of miR-125a's effects in thyroiditis.
  • miR-125a represents a potential therapeutic target for managing thyroiditis.
Keywords:
inflammationmicroRNA-125aphosphoinositide 3-kinase/protein kinase B/mechanical target of rampamycinthyroiditis

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