Aldeli Nour, Hanano Abdulsamie
Department of Animal Biology, Faculty of science, Al Furat University, Deir-ez-Zor, Syria.
Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria (AECS), Damascus, Syria.
Reprod Toxicol. 2025 Mar;132:108863. doi: 10.1016/j.reprotox.2025.108863. Epub 2025 Feb 18.
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.
2,3,7,8-四氯二苯并对二恶英（TCDD）是迄今为止已知的最具毒性的有机环境污染物，被公认为是一种人类致癌物。尽管已有文献记载哺乳动物雌性个体中TCDD暴露与上皮性卵巢癌（EOC）之间存在联系，但癌症起始的分子机制仍不清楚。新出现的证据表明，包括卵巢癌（OC）在内的各种人类恶性肿瘤中存在异常的miRNA表达。本研究旨在探讨雌性小鼠暴露于TCDD是否会扰乱miRNA的表达，特别是那些已知的OC调节因子。我们在PubMed数据库中进行了广泛搜索，以鉴定实验证明与OC相关的miRNA。共鉴定出52种miRNA作为潜在的OC调节因子，并根据它们在OC中的丰度分为两组。第一组包括24种在OC中上调的miRNA，而第二组包括28种在OC中下调的miRNA。随后，我们分析了单次给予TCDD剂量后BALB/c小鼠卵巢中两组miRNA的表达情况。我们的研究结果显示，第一组中的10种miRNA（miR-21、miR-27a、miR-30a、miR-99a、miR-141、miR-182、miR-183、miR-200a、miR-200b和miR-429）显著上调，第二组中的12种miRNA（let-7d、miR-15a、miR-19a、miR-23b、miR-34a、miR-34c、miR-125b-1、miR-133、miR-140、miR-199a、miR-210和miR-383）在暴露于TCDD的小鼠卵巢中显著下调。此外，我们通过在PubMed数据库中广泛搜索，确定了两组miRNA靶向的OC相关基因。使用TR-qPCR，我们评估了TCDD失调的miRNA对其靶基因的下游影响。我们的结果表明，TCDD诱导的致癌miRNA上调对与EOC相关的靶基因产生负调控，而癌症抑制miRNA的下调则对与EOC相关的基因产生正调控。
