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Non-coding RNA genes modulate PI3K/AKT signaling pathway in polycystic ovary syndrome

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Abstract

Background

The PI3K protein kinase B (PI3K/AKT) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. The purpose of this study is to validate the association of PCOS with PI3K/AKT pathway target genes, miRNA486-5p, and miRNA483-5p as well as to evaluate the outcome of metformin on the pathogenesis of PCOS. 

Methods

This case-controlled study included 3 subject groups: twenty healthy females (control group), twenty PCOS females before treatment, and twenty PCOS females treated with metformin at a dose (500 mg 3 times per day for 3 months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miRNA486-5p, and miRNA483-5p in the whole blood.

Results

There was a significant decrease in miRNA486-5p and miRNA483-5p in the PCOS group with a significant negative correlation between miRNA486-5p and PI3K and a significant negative correlation between miRNA483-5p and ERK. Metformin treatment resulted in significant elevation of the studied miRNA, significant downregulation of PI3K/AKT target genes, and significant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression.

Conclusions

miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, influence glucose metabolism, and result in IR in PCOS. Metformin’s upregulation of those miRNAs affects glucose metabolism by controlling the expression of GLUT4, ameliorates PCOS-related insulin resistance, and improves PCOS-related hormonal imbalance by controlling the PI3K/AKT signaling pathway.

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Data availability

The data used and/or analyzed during this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to the patients for their contribution to this study and the authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by the Grant Code: (23UQU4331391DSR002).

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, Cairo, 11562, Egypt

    Heba S. Omar, Hanan Fouad & Miriam safwat

  2. Obstetrics and Gynecology Department, Faculty of Medicine, Minia University, Minya, Egypt

    Osama Ahmed Ibrahim

  3. Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt

    Maha Gomaa sayed

  4. Anatomy Department, College of Medicine, Umm Al-Qura University, Makkah, 24382, Saudi Arabia

    Eman Mohammed Faruk

  5. Faculty of Medicine, Galala University, POB 43711, Attaka, Egypt

    Hanan Fouad

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  1. Heba S. Omar
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  4. Eman Mohammed Faruk
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Contributions

HSO participated in the debate and wrote the initial manuscript, figure legends, text descriptions of the histology observations, and interpretations. OA performed biochemical and gene investigations, analysis, and interpretation, while MS took part in the manuscript’s writing and data search. MG took part in the biochemical analysis, connected the research data, and produced the paper’s final draft. HF and EM gathered information from the literature and carried out the morphometric analysis, investigation, and result correlation. The final draft of the work was approved by all authors.

Corresponding author

Correspondence to Eman Mohammed Faruk.

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Conflict of interest

The authors have no conflicts of interest or other disclosures to report.

Ethical approval

The study was designed and conducted according to ethical norms approved by the Local Ethics Committee of Cairo University, Faculty of Medicine, and written informed consent from all females (IRB number (MD-284-2020).

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Omar, H.S., Ibrahim, O.A., sayed, M.G. et al. Non-coding RNA genes modulate PI3K/AKT signaling pathway in polycystic ovary syndrome. Mol Biol Rep 50, 8361–8372 (2023). https://doi.org/10.1007/s11033-023-08604-0

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