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Formononetin promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in

Jian Chen1, Xing Zhang1, Yong Wang1

  • 1School of Basic Medical Sciences, Guilin Medical University, Guilin, China.

Molecular Carcinogenesis
|February 10, 2015
PubMed

Insights

Formononetin, found in Astragalus membranaceus, promotes estrogen receptor alpha-positive cell proliferation. This effect is mediated by activating miR-375, potentially through a feedback loop with ERα.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Formononetin is an isoflavone from Astragalus membranaceus with known antitumorigenic effects.
  • Previous research indicated formononetin induces growth inhibition and apoptosis in MCF-7 breast cancer cells.

Purpose of the Study:

  • To investigate formononetin's role in promoting cell proliferation in estrogen receptor (ER)-positive cells.
  • To elucidate the underlying molecular mechanisms of formononetin's proliferative effects.

Main Methods:

  • In vitro studies utilized ERα-positive HUVEC and MCF-7 cells treated with formononetin.
  • Cell proliferation and apoptosis were assessed using CCK8 assay, Hoechst 33258, and flow cytometry.
  • Gene and protein expression (ERα, Bcl-2, miR-375, p-Akt) were analyzed via real-time PCR and Western blot; in vivo studies used ovariectomized mice.

Main Results:

  • Low concentrations of formononetin (2-6 μM) significantly stimulated proliferation in ERα-positive HUVEC and MCF-7 cells.
  • Formononetin treatment upregulated ERα, miR-375, p-Akt, and Bcl-2 expression.
  • The proliferative effect was inhibited by a miR-375 inhibitor or raloxifene; in vivo uterine weight increase was also blocked by these inhibitors.

Conclusions:

  • Formononetin promotes ERα-positive cell proliferation via miR-375 activation.
  • The mechanism likely involves a feedback loop between miR-375 and ERα.
  • These findings suggest a novel pathway for formononetin's action in ERα-positive cells.
Keywords:
AktERαHUVECformononetinmiR-375

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