RGD Reference Report - Downregulation of MicroRNA-222 Reduces Insulin Resistance in Rats with PCOS by Inhibiting Activation of the MAPK/ERK Pathway via Pten. - Rat Genome Database

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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.

Authors: Ye, Hong  Liu, Xiu-Juan  Hui, Yan  Liang, Yang-Huan  Li, Cai-Hong  Wan, Qiong 
Citation: Ye H, etal., Mol Ther Nucleic Acids. 2020 Jul 10;22:733-741. doi: 10.1016/j.omtn.2020.07.014. eCollection 2020 Dec 4.
RGD ID: 151893462
Pubmed: PMID:33230470   (View Abstract at PubMed)
PMCID: PMC7593506   (View Article at PubMed Central)
DOI: DOI:10.1016/j.omtn.2020.07.014   (Journal Full-text)

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.



Disease Annotations    

Gene Ontology Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Mir222  (microRNA 222)

Genes (Mus musculus)
Mir222  (microRNA 222)

Genes (Homo sapiens)
MIR222  (microRNA 222)


Additional Information