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Article: Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis

TitleEnvironmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis
Authors
Keywordsbisphenol A
cancer stem cells
microRNA
oestrogen receptors
ovarian cancer
Issue Date1-Sep-2023
PublisherWiley Open Access
Citation
Journal of Cellular and Molecular Medicine, 2023, v. 27, n. 18, p. 2792-2803 How to Cite?
Abstract

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.


Persistent Identifierhttp://hdl.handle.net/10722/338677
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 1.207
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLam, SSN-
dc.contributor.authorShi, Z-
dc.contributor.authorIp, CKM-
dc.contributor.authorWong, CKC-
dc.contributor.authorWong, AST-
dc.date.accessioned2024-03-11T10:30:42Z-
dc.date.available2024-03-11T10:30:42Z-
dc.date.issued2023-09-01-
dc.identifier.citationJournal of Cellular and Molecular Medicine, 2023, v. 27, n. 18, p. 2792-2803-
dc.identifier.issn1582-1838-
dc.identifier.urihttp://hdl.handle.net/10722/338677-
dc.description.abstract<p>Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.</p>-
dc.languageeng-
dc.publisherWiley Open Access-
dc.relation.ispartofJournal of Cellular and Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectbisphenol A-
dc.subjectcancer stem cells-
dc.subjectmicroRNA-
dc.subjectoestrogen receptors-
dc.subjectovarian cancer-
dc.titleEnvironmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis-
dc.typeArticle-
dc.identifier.doi10.1111/jcmm.17920-
dc.identifier.scopuseid_2-s2.0-85168562847-
dc.identifier.volume27-
dc.identifier.issue18-
dc.identifier.spage2792-
dc.identifier.epage2803-
dc.identifier.eissn1582-4934-
dc.identifier.isiWOS:001052682100001-
dc.identifier.issnl1582-1838-

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