Role of metformin in functional endometrial hyperplasia and polycystic ovary syndrome involves the regulation of MEG3/miR223/GLUT4 and SNHG20/miR4486/GLUT4 signaling.
Mol Med Rep
; 26(1)2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35552758
ABSTRACT
Metformin (MET) can effectively treat endometrial hyperplasia (EH), and the expression of glucose transporter type 4 insulinresponsive (GLUT4) is closely associated with the development of EH. The present study aimed to verify the effect of MET in functional EH and polycystic ovary syndrome (PCOS). H&E staining was performed to analyze the severity of EH, and immunohistochemistry was performed to evaluate the expression of GLUT4 in the endometrium of PCOS rats. Reverse transcriptionquantitative PCR was used to calculate the expression of long noncoding (lnc)RNAmaternally expressed gene 3 (MEG3), lncRNAsmall nucleolar RNA host gene 20 (SNHG20), GLUT4 mRNA, microRNA (miR)223 and miR4486. Sequence analysis and luciferase assays were performed to explore the regulatory relationship among certain lncRNAs, miRNAs and target genes. EH in PCOS rats was efficiently inhibited by MET administration. The increased expression of GLUT4 in PCOS rats was attenuated by MET treatment. Moreover, the expression levels of lncRNAMEG3 and lncRNASNHG20 were significantly inhibited in the endometrium of PCOS rats. MET treatment also showed remarkable efficiency in restoring the expression of lncRNAMEG3 and lncRNASNHG20. Meanwhile, the expression levels of miR223 and miR4486 were notably elevated in the endometrium of PCOS rats, while MET treatment reduced the expression of miR223 and miR4486 in PCOS rats. Furthermore, a luciferase assay confirmed the inhibitory relationship between miR223 and lncRNAMEG3/GLUT4 expression, as well as between miR4486 and lncRNASNHG20/GLUT4 expression. GLUT4 knockdown restored the decreased viability of HCC94 cells induced by overexpression of lncRNAMEG3. To conclude, MET exhibited a therapeutic effect in the treatment of EH by modulating the lncRNAMEG3/miR223/GLUT4 and lncRNASNHG20/miR4486/GLUT4 signaling pathways. This work provides mechanistic insight into the development of EH.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Ovário Policístico
/
Carcinoma Hepatocelular
/
MicroRNAs
/
Hiperplasia Endometrial
/
RNA Longo não Codificante
/
Neoplasias Hepáticas
/
Metformina
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article