MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency

Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea that lasts for a minimum of four months in women < 40 years old and is typically characterized by reduced estrogen levels and elevated serum concentrations of follicle-stimulating hormone. We collected urine samples from tw...

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Main Authors: Zobia Umair, Mi-Ock Baek, Jisue Song, Seona An, Seung Joo Chon, Mee-Sup Yoon
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/18/2797
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author Zobia Umair
Mi-Ock Baek
Jisue Song
Seona An
Seung Joo Chon
Mee-Sup Yoon
author_facet Zobia Umair
Mi-Ock Baek
Jisue Song
Seona An
Seung Joo Chon
Mee-Sup Yoon
author_sort Zobia Umair
collection DOAJ
description Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea that lasts for a minimum of four months in women < 40 years old and is typically characterized by reduced estrogen levels and elevated serum concentrations of follicle-stimulating hormone. We collected urine samples from two participant cohorts from Gil Hospital of Gachon University (Incheon, Korea): a sequencing cohort of 19 participants (seven patients with POI (POI patients without Turner syndrome), seven patients with Turner syndrome (POI patients with Turner syndrome), and five control individuals (age-matched controls with confirmed ovarian sufficiency)) and a validation cohort of 46 participants (15 patients with POI, 11 patients with Turner syndrome, and 20 control individuals). Among differentially expressed miRNAs, hsa-miR-4516 was significantly upregulated in patients with POI in both cohorts, independent of the presence of Turner syndrome. Moreover, the upregulation of miR-4516 was confirmed in the ovary—but not in the uterus—of a cyclophosphamide and busulfan-induced POI mouse model. This was accompanied by a decrease in STAT3 protein level, a predicted target of miR-4516, via miRTarBase2020. Our study provides compelling evidence that miR-4516 is highly expressed in patients with POI and POI mouse models, suggesting that miR-4516 is a diagnostic marker of POI.
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spelling doaj.art-1dab056878cf4f7b926734fde16404562023-11-23T15:32:22ZengMDPI AGCells2073-44092022-09-011118279710.3390/cells11182797MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian InsufficiencyZobia Umair0Mi-Ock Baek1Jisue Song2Seona An3Seung Joo Chon4Mee-Sup Yoon5Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 21999, KoreaDepartment of Molecular Medicine, School of Medicine, Gachon University, Incheon 21999, KoreaGachon University Gil Medical Center, Department of Obstetrics and Gynecology, College of Medicine, Gachon University, Incheon 21565, KoreaGachon University Gil Medical Center, Department of Obstetrics and Gynecology, College of Medicine, Gachon University, Incheon 21565, KoreaGachon University Gil Medical Center, Department of Obstetrics and Gynecology, College of Medicine, Gachon University, Incheon 21565, KoreaDepartment of Molecular Medicine, School of Medicine, Gachon University, Incheon 21999, KoreaPremature ovarian insufficiency (POI) is a typical disorder of amenorrhea that lasts for a minimum of four months in women < 40 years old and is typically characterized by reduced estrogen levels and elevated serum concentrations of follicle-stimulating hormone. We collected urine samples from two participant cohorts from Gil Hospital of Gachon University (Incheon, Korea): a sequencing cohort of 19 participants (seven patients with POI (POI patients without Turner syndrome), seven patients with Turner syndrome (POI patients with Turner syndrome), and five control individuals (age-matched controls with confirmed ovarian sufficiency)) and a validation cohort of 46 participants (15 patients with POI, 11 patients with Turner syndrome, and 20 control individuals). Among differentially expressed miRNAs, hsa-miR-4516 was significantly upregulated in patients with POI in both cohorts, independent of the presence of Turner syndrome. Moreover, the upregulation of miR-4516 was confirmed in the ovary—but not in the uterus—of a cyclophosphamide and busulfan-induced POI mouse model. This was accompanied by a decrease in STAT3 protein level, a predicted target of miR-4516, via miRTarBase2020. Our study provides compelling evidence that miR-4516 is highly expressed in patients with POI and POI mouse models, suggesting that miR-4516 is a diagnostic marker of POI.https://www.mdpi.com/2073-4409/11/18/2797urinary exosomemicro-RNApremature ovarian insufficiencyhsa-miR-4516turner syndrome
spellingShingle Zobia Umair
Mi-Ock Baek
Jisue Song
Seona An
Seung Joo Chon
Mee-Sup Yoon
MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
Cells
urinary exosome
micro-RNA
premature ovarian insufficiency
hsa-miR-4516
turner syndrome
title MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
title_full MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
title_fullStr MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
title_full_unstemmed MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
title_short MicroRNA-4516 in Urinary Exosomes as a Biomarker of Premature Ovarian Insufficiency
title_sort microrna 4516 in urinary exosomes as a biomarker of premature ovarian insufficiency
topic urinary exosome
micro-RNA
premature ovarian insufficiency
hsa-miR-4516
turner syndrome
url https://www.mdpi.com/2073-4409/11/18/2797
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