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

Sophia S. N. Lam, Zeyu Shi, Carman K. M. Ip, Chris K. C. Wong, Alice S. T. Wong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


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.

Original languageEnglish
Pages (from-to)2792-2803
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Issue number18
Early online date23 Aug 2023
Publication statusPublished - Sept 2023

Scopus Subject Areas

  • Molecular Medicine
  • Cell Biology

User-Defined Keywords

  • bisphenol A
  • cancer stem cells
  • microRNA
  • oestrogen receptors
  • ovarian cancer


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