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Downregulation of MicroRNA-222 Reduces Insulin Resistance in Rats with PCOS by Inhibiting Activation of the MAPK/ERK Pathway via Pten.

Abstract：

:Polycystic ovary syndrome (PCOS), characterized by the dysfunction of endocrine metabolism, is a common disease among women. Insulin (INS) resistance (IR) is considered as an obstruction to effective PCOS treatment. Here, we aimed to explore the mechanism by which microRNA-222 (miR-222) affects IR in PCOS via Pten. Quantitative reverse transcription-polymerase chain reaction and western blot assays indicated that miR-222 expression was higher in the peripheral blood of PCOS patients with IR than in PCOS patients without IR, while Pten expression was lower. Further mechanistic analysis identified Pten as a target gene of miR-222. Moreover, PCOS rat models were established through the administration of dehydroepiandrosterone and were subsequently treated with miR-222 agomir, miR-222 antagomir, or Pten overexpression plasmid. The inhibition of miR-222 improved ovarian morphology, enhanced the production of serum sex hormones (follicle-stimulating hormone [FSH], luteotropic hormone [LH], estradiol 2 [E2], prolactin [PRL], and testosterone [T]), increased the levels of glucose metabolism indicators (homeostasis model of assessment for IR [HOMA-IR], blood glucose [BG]120min, and INS120min), and reduced the production of progesterone in the PCOS rats. Notably, miR-222 downregulation resulted in the inactivation of the mitogen-activated protein kinase (MAPK)/ERK pathway by upregulating Pten. Collectively, miR-222 inhibition might reduce IR in PCOS by inactivating the MAPK/ERK pathway and elevating Pten expression, which indicates miR-222 as a promising target for PCOS treatment.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Ye H,Liu XJ,Hui Y,Liang YH,Li CH,Wan Q

doi

10.1016/j.omtn.2020.07.014

subject

Has Abstract

pub_date

2020-07-10 00:00:00

pages

733-741

issn

2162-2531

pii

S2162-2531(20)30203-1

journal_volume

22

pub_type

杂志文章

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