Integrated In-Silico and In Vitro analysis to Decipher the contribution of bisphenol-A in cervical cancer

• Published in: Toxicology (Amsterdam) Vol. 504; p. 153791
• Main Authors: Khan, Nadeem Ghani, Adiga, Divya, Rai, Padmalatha Satwadi, Kabekkodu, Shama Prasada
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2024
• Subjects: Bisphenol A; Carcinogen; Drug repurposing; Endocrine disruptor; Environmental toxicant; Human cancer; PPIN; Human cancer; TCF/LEF; Drug repurposing; DOC2B; EGFR; YY1; BSA; CDH2; CCND1; TACCO; BAPTA; Environmental toxicant; CC; PBS; WNT5A; Endocrine disruptor; EMT; MTOR; TCGA; VEGFA; Carcinogen; Bisphenol A; BPA; CTD; Ca2; CCNE1; ROS; BIRC5; CAPS8; CTNNB1; DCFDA; VIM; FGFR3
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2024.153791

Bisphenol A (BPA) is a synthetic chemical widely used as a monomer for producing polycarbonate plastics. The present investigation employed an in-silico approach to identify BPA-responsive genes and comprehend the biological functions affected using in vitro studies. A Comparative Toxicogenomics Database search identified 29 BPA-responsive genes in cervical cancer (CC). Twenty-nine genes were screened using published datasets, and thirteen of those showed differential expression between normal and CC samples. Protein-Protein Interaction Networks (PPIN) analysis identified BIRC5, CASP8, CCND1, EGFR, FGFR3, MTOR, VEGFA, DOC2B, WNT5A, and YY1 as hub genes. KM-based survival analysis identified that CCND, EGFR, VEGFA, FGFR3, DOC2B, and YY1 might affect CC patient survival. SiHa and CaSki cell proliferation, migration, and invasion were all considerably accelerated by BPA exposure. Changes in cell morphology, remodeling of the actin cytoskeleton, increased number and length of filopodia, elevated intracellular reactive oxygen species and calcium, and lipid droplet accumulation were noted upon BPA exposure. BPA treatment upregulated the expression of epithelial to mesenchymal transition pathway members and enhanced the nuclear translocation of CTNNB1. We showed that the enhanced migration and nuclear translocation of CTNNB1 upon BPA exposure is a calcium-dependent process. The present study identified potential BPA-responsive genes and provided novel insights into the biological effects and mechanisms affected by BPA in CC. Our study raises concern over the use of BPA. [Display omitted]