Clinical and Experimental Reproductive Medicine

  • 제47권3호
  • /
  • Pages.194-206
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  • 2020
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
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miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon (Department of Biomedical Science, College of Life Science, Institute of Reproductive Medicine, CHA University) ;
  • Kang, Youn-Jung (Department of Biomedical Science, College of Life Science, Institute of Reproductive Medicine, CHA University) ;
  • Kwon, Jinie (Department of Biomedical Science, College of Life Science, Institute of Reproductive Medicine, CHA University) ;
  • Nishi, Yoshihiro (Department of Physiology, Kurume University School of Medicine) ;
  • Yanase, Toshihiko (Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University) ;
  • Lee, Kyung-Ah (Department of Biomedical Science, College of Life Science, Institute of Reproductive Medicine, CHA University) ;
  • Koong, Mi Kyoung (Department of Obstetrics and Gynecology, CHA University, Fertility Center, CHA General Hospital)
  • 투고 : 2019.11.08
  • 심사 : 2020.03.23
  • 발행 : 2020.09.30
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초록

Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

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참고문헌

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