4.7 Article

Effects of bisphenol A on uterine leiomyoma: In vitro and in vivo evaluation with mechanistic insights related to XBP1

Journal

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 247, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.114201

Keywords

RNA-seq; ChIP-seq; XBP1; Bisphenol A; Uterine leiomyoma

Funding

  1. National Natural Science Founda- tion of China
  2. [81673130]
  3. [82072078]

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This study found that BPA can promote the proliferation of uterine leiomyomas by regulating the transcription factor XBP1 and activating the PI3K/AKT signaling pathway. The study reveals the pathogenesis associated with exposure to BPA and other endocrine disruptors and identifies XBP1 as an important regulator and potential therapeutic target for uterine leiomyomas.
The incidence rate of human uterine leiomyomas is over 70% in the women of childbearing age, which has caused serious health and financial burden. Our previous study confirmed that Bisphenol A (BPA),representative environmental estrogen, promoted the proliferation of human uterine leiomyomas and up-regulated the expression of cell proliferation-related genes. In this study, by combining ChIP-seq and RNA-seq, it was shown that after BPA intervention, H3K27ac modification levels and gene expression levels were altered in uterine leiomyomas cells. Moreover experimental verification found that BPA can regulate ITGA2 through the transcription factor XBP1, activate the downstream PI3K/AKT signaling pathway, eventually promote the proliferation of uterine leiomyomas. The present study provides new insights into the pathogenesis associated with exposure to BPA and other endocrine disruptors with similar effects by defining XBP1 as an important regulator, and which may act as an intervention and treatment target for uterine leiomyomas.

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