Article ; Online: Integrated In-Silico and In Vitro analysis to Decipher the contribution of bisphenol-A in cervical cancer.
2024 Volume 504, Page(s) 153791
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Humans ; Phenols/toxicity ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/metabolism ; Benzhydryl Compounds/toxicity ; Female ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Computer Simulation ; Gene Expression Regulation, Neoplastic/drug effects ; Cell Line, Tumor ; Protein Interaction Maps ; Epithelial-Mesenchymal Transition/drug effects |
| Chemical Substances | Phenols ; bisphenol A (MLT3645I99) ; Benzhydryl Compounds |
| Language | English |
| Publishing date | 2024-03-29 |
| Publishing country | Ireland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 184557-3 |
| ISSN | 1879-3185 ; 0300-483X |
| ISSN (online) | 1879-3185 |
| ISSN | 0300-483X |
| DOI | 10.1016/j.tox.2024.153791 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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