Comparative analysis of transcriptomic changes induced by zearalenone and bisphenol A in human ovarian cancer cells

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log2FC > 1); 292, 260 and 45 genes were downregulated (log2FC < -1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log2FC > 1, or log2FC < -1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells. The PEO1 human epithelial ovarian cell line was treated with 10 nM estradiol, 10 nM zearalenone and 100 nM bisphenol A. A non-treated control was also included as a negative control that was faced to the same culturing conditions except estrogen treatment. Total RNA was isolated 8 h-s after the treatment. Global transcriptomic profile was studied by RNA-sequencing applying the Illumina NextSeq500 platform including both mRNA and microRNA sequencing. In the case of all the samples 3 replicates were included. In order to identify up-, or down-regulated genes and microRNAs the treated samples were compared to the non-treated control samples.