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.
摘要：
双酚A(BPA)是广泛用作生产聚碳酸酯塑料的单体的合成化学品。本研究采用计算机内方法来鉴定BPA响应基因，并使用体外研究了解受影响的生物学功能。比较毒性基因组学数据库搜索在宫颈癌（CC）中确定了29个BPA响应基因。使用已发布的数据集筛选了29个基因，其中13例显示正常和CC样品之间的差异表达。蛋白质-蛋白质相互作用网络(PPIN)分析确定了BIRC5、CASP8、CCND1、EGFR、FGFR3,MTOR,VEGFA,DOC2B,WNT5A,和YY1作为hub基因。基于KM的生存分析确定CCND，EGFR,VEGFA,FGFR3,DOC2B,YY1可能影响CC患者的生存率。SiHa和CaSki细胞增殖，迁移,BPA暴露大大加速了入侵。细胞形态的变化，肌动蛋白细胞骨架的重塑，丝伪足的数量和长度增加，细胞内活性氧和钙升高，在BPA暴露后注意到脂滴积累。BPA处理上调上皮至间充质转化通路成员的表达并增强CTNNB1的核转位。我们表明，BPA暴露后CTNNB1的迁移和核易位增强是钙依赖性过程。本研究确定了潜在的BPA响应基因，并为CC中BPA影响的生物学效应和机制提供了新的见解。我们的研究引起了人们对BPA使用的关注。
