Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, yet its underlying mechanisms remain incompletely understood. This study investigated the role of hsa_circ_0020491 in PCOS pathogenesis, focusing on granulosa cells (GCs). Analysis of GCs from PCOS patients and controls rev...

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Main Authors: XiaLing Huang, Fen Yu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gynecological Endocrinology
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Online Access:https://www.tandfonline.com/doi/10.1080/09513590.2025.2536579
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author XiaLing Huang
Fen Yu
author_facet XiaLing Huang
Fen Yu
author_sort XiaLing Huang
collection DOAJ
description Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, yet its underlying mechanisms remain incompletely understood. This study investigated the role of hsa_circ_0020491 in PCOS pathogenesis, focusing on granulosa cells (GCs). Analysis of GCs from PCOS patients and controls revealed significant upregulation of both hsa_circ_0020491 and IGF2BP2, with their expression levels positively correlated. In a dihydrotestosterone (DHT)-treated KGN cell model of PCOS, silencing either circ_0020491 or IGF2BP2 mitigated autophagy dysregulation and mitochondrial dysfunction, evidenced by altered autophagy-related proteins, mitochondrial membrane potential, ATP levels, mtDNA content, and reactive oxygen species. Mechanistically, circ_0020491 binds to and stabilizes IGF2BP2, amplifying its effects. Overexpression of IGF2BP2 counteracted the improvements induced by circ_0020491 knockdown. In vivo, a dehydroepiandrosterone (DHEA)-induced PCOS mouse model confirmed that circ_0020491 suppression attenuated disease progression, improved mitochondrial function, and reduced excessive autophagy. These findings demonstrate that hsa_circ_0020491 exacerbates PCOS by interacting with IGF2BP2 to disrupt autophagy and mitochondrial homeostasis in GCs, offering a potential therapeutic target.
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spelling doaj-art-deaed054c400403e89855509038780242025-08-20T02:46:24ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662025-12-0141110.1080/09513590.2025.2536579Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunctionXiaLing Huang0Fen Yu1Department Of gynecology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, ChinaDepartment Of gynecology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, ChinaPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, yet its underlying mechanisms remain incompletely understood. This study investigated the role of hsa_circ_0020491 in PCOS pathogenesis, focusing on granulosa cells (GCs). Analysis of GCs from PCOS patients and controls revealed significant upregulation of both hsa_circ_0020491 and IGF2BP2, with their expression levels positively correlated. In a dihydrotestosterone (DHT)-treated KGN cell model of PCOS, silencing either circ_0020491 or IGF2BP2 mitigated autophagy dysregulation and mitochondrial dysfunction, evidenced by altered autophagy-related proteins, mitochondrial membrane potential, ATP levels, mtDNA content, and reactive oxygen species. Mechanistically, circ_0020491 binds to and stabilizes IGF2BP2, amplifying its effects. Overexpression of IGF2BP2 counteracted the improvements induced by circ_0020491 knockdown. In vivo, a dehydroepiandrosterone (DHEA)-induced PCOS mouse model confirmed that circ_0020491 suppression attenuated disease progression, improved mitochondrial function, and reduced excessive autophagy. These findings demonstrate that hsa_circ_0020491 exacerbates PCOS by interacting with IGF2BP2 to disrupt autophagy and mitochondrial homeostasis in GCs, offering a potential therapeutic target.https://www.tandfonline.com/doi/10.1080/09513590.2025.2536579Polycystic ovary syndromehsa_circ_0020491IGF2BP2granular cellsautophagymitochondria
spellingShingle XiaLing Huang
Fen Yu
Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
Gynecological Endocrinology
Polycystic ovary syndrome
hsa_circ_0020491
IGF2BP2
granular cells
autophagy
mitochondria
title Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
title_full Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
title_fullStr Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
title_full_unstemmed Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
title_short Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction
title_sort hsa circ 0020491 promotes polycystic ovary syndrome by interacting with igf2bp2 through regulation of granular cell autophagy and mitochondrial dysfunction
topic Polycystic ovary syndrome
hsa_circ_0020491
IGF2BP2
granular cells
autophagy
mitochondria
url https://www.tandfonline.com/doi/10.1080/09513590.2025.2536579
work_keys_str_mv AT xialinghuang hsacirc0020491promotespolycysticovarysyndromebyinteractingwithigf2bp2throughregulationofgranularcellautophagyandmitochondrialdysfunction
AT fenyu hsacirc0020491promotespolycysticovarysyndromebyinteractingwithigf2bp2throughregulationofgranularcellautophagyandmitochondrialdysfunction