Unveiling the transcriptional pattern of epithelial ovarian carcinoma-related microRNAs-mRNAs network after mouse exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent organic environmental contaminant known to date, is recognized as a human carcinogen. Despite the documented link between TCDD exposure and epithelial ovarian cancer (EOC) in mammalian females, the molecular mechanisms underlying cancer initiation remain elusive. Emerging evidence suggests aberrant miRNA expression in various human malignancies, including OC. This work was performed to examine whether TCDD exposure in female mice disrupts the expression of miRNAs, particularly those known as OC-modulators. We conducted an extensive search in the PubMed database to identify miRNAs experimentally implicated in OC. Fifty-two miRNAs were identified as potential OC modulators and classified into two groups based on their abundance in OC. Group I comprised 24 miRNAs upregulated in OC, while Group II included 28 miRNAs downregulated in OC. Subsequently, we analyzed the expression of both groups in BALB/c mice ovaries following a single TCDD dose. Our findings revealed significant upregulation of 10 miRNAs from Group I (miR-21, miR-27a, miR-30a, miR-99a, miR-141, miR-182, miR-183, miR-200a, miR-200b, and miR-429) and significant downregulation of 12 miRNAs from Group II (let-7d, miR-15a, miR-19a, miR-23b, miR-34a, miR-34c, miR-125b-1, miR-133, miR-140, miR-199a, miR-210, and miR-383) in TCDD-exposed mouse ovaries. Furthermore, we identified OC-related genes targeted by miRNAs from both groups through an extensive search in PubMed databases. Using TR-qPCR, we evaluated the downstream impact of TCDD-dysregulated miRNAs on their target genes. Our results indicate that TCDD-induced upregulation of oncogenic miRNAs negatively regulates target genes associated with EOC, while downregulation of cancer-suppressor miRNAs positively regulates genes linked to EOC.