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miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

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...

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Autores principales: Lee, Su-Yeon, Kang, Youn-Jung, Kwon, Jinie, Nishi, Yoshihiro, Yanase, Toshihiko, Lee, Kyung-Ah, Koong, Mi Kyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Reproductive Medicine 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482943/
https://www.ncbi.nlm.nih.gov/pubmed/32854459
http://dx.doi.org/10.5653/cerm.2019.03412
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author Lee, Su-Yeon
Kang, Youn-Jung
Kwon, Jinie
Nishi, Yoshihiro
Yanase, Toshihiko
Lee, Kyung-Ah
Koong, Mi Kyoung
author_facet Lee, Su-Yeon
Kang, Youn-Jung
Kwon, Jinie
Nishi, Yoshihiro
Yanase, Toshihiko
Lee, Kyung-Ah
Koong, Mi Kyoung
author_sort Lee, Su-Yeon
collection PubMed
description 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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spelling pubmed-74829432020-09-21 miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone Lee, Su-Yeon Kang, Youn-Jung Kwon, Jinie Nishi, Yoshihiro Yanase, Toshihiko Lee, Kyung-Ah Koong, Mi Kyoung Clin Exp Reprod Med Original Article 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. Korean Society for Reproductive Medicine 2020-09 2020-08-28 /pmc/articles/PMC7482943/ /pubmed/32854459 http://dx.doi.org/10.5653/cerm.2019.03412 Text en Copyright © 2020. THE KOREAN SOCIETY FOR REPRODUCTIVE MEDICINE This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Su-Yeon
Kang, Youn-Jung
Kwon, Jinie
Nishi, Yoshihiro
Yanase, Toshihiko
Lee, Kyung-Ah
Koong, Mi Kyoung
miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title_full miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title_fullStr miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title_full_unstemmed miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title_short miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
title_sort mir-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482943/
https://www.ncbi.nlm.nih.gov/pubmed/32854459
http://dx.doi.org/10.5653/cerm.2019.03412
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