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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
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An integrated in silico analysis highlighted angiogenesis regulating miRNA-mRNA network in PCOS pathophysiology.
Krutika Patil1, Shaini Joseph2, Jatin Shah3
1Department of Molecular Endocrinology, Indian Council of Medical Research-National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai, 400012, India.
Journal of Assisted Reproduction and Genetics
|January 15, 2022
Summary
Polycystic ovary syndrome (PCOS) involves altered ovarian angiogenesis. This study identified key microRNAs (miRNAs) and pathways, like PI3K/Akt signaling, that regulate angiogenesis in PCOS, offering insights into infertility causes.
Area of Science:
- Reproductive Endocrinology
- Molecular Biology
- Genomics
Background:
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder causing anovulatory infertility.
- Angiogenesis, crucial for ovarian follicle development, is dysregulated in PCOS.
- Limited understanding exists regarding microRNAs (miRNAs) controlling angiogenesis-related genes in PCOS ovaries.
Purpose of the Study:
- Identify dysregulated angiogenesis-related genes in PCOS ovaries.
- Determine miRNAs that regulate these genes.
- Construct a regulatory network of miRNA-mRNA interactions in PCOS angiogenesis.
Main Methods:
- Reanalyzed PCOS ovarian gene expression datasets (GEO).
- Predicted miRNA targets using databases and verified ovarian expression.
- Utilized Panther and STRING for pathway enrichment analysis.
- Quantified miRNA expression in granulosa cells via digital droplet PCR.
Main Results:
- Identified miRNAs targeting dysregulated angiogenesis genes in PCOS.
- Shortlisted pathways including VEGF, FGF, PI3K/Akt, Notch, and ECM interaction.
- PI3K/Akt signaling emerged as the most enriched pathway.
- Found miR-218-5p, miR-214-3p, miR-20a-5p, and miR-140-3p upregulated in PCOS granulosa cells, linked to PI3K/Akt.
Conclusions:
- Identified key angiogenesis-related genes and miRNA-mRNA interactions in PCOS via in silico analysis.
- Highlighted the role of PI3K/Akt signaling in impaired follicular angiogenesis in PCOS.
- Provided novel insights into the mechanisms of aberrant ovarian angiogenesis in PCOS pathophysiology.
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