Identification of key genes linking bisphenols exposure and breast cancer

Abstract

Breast cancer (BC) is one of the most common types of cancer and is caused by the complex interplay of genetic and environmental factors, such as an unhealthy lifestyle, family history of illness, reproductive factors, and ageing. However, increasing evidence has revealed that manufactured organic pollutants such as bisphenols are closely related to BC. Bisphenols exposure can promote the progression of BC through multiple complicated and variable molecular mechanisms. Reanalysis of existing data on this topic may reveal molecular markers with clinical value. In this study, we identified four key genes [keratin 14 (KRT14), keratin 5 (KRT5), acyl-CoA synthetase long chain family member 1 (ACSL1) and matrix metallopeptidase 1 (MMP1)] related to both bisphenols exposure and BC by employing the Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas Cervical Cancer (TCGA-CESC) dataset; notably, KRT14 expression exhibited the most significant difference between tumour and normal tissues. Further analysis of the functions and biological processes associated with KRT14 and related regulatory molecules revealed that bisphenols exposure induces BC-promoting characteristics and aggressive behaviour-related signaling pathways, such as the steroid biosynthesis, Forkhead box (FOXO) and prolactin signaling pathways. To confirm the expression and biological effects of KRT14, we conducted relevant experiments. In vitro studies revealed that bisphenols such as bisphenol A (BPA) exposure significantly affected the proliferation, migration, and invasion of MCF-7 cells by inhibiting KRT14 expression. Similarly, we also observed a decrease in KRT14 expression in BPA induced abnormal breast tissue in mice. In summary, our study revealed potential genes and pathways associated with bisphenols exposure in BC.