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首页> 外文期刊>Biochemistry >Expression of hormonal carcinogenesis genes and related regulatory microRNAs in uterus and ovaries of DDT-treated female rats
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Expression of hormonal carcinogenesis genes and related regulatory microRNAs in uterus and ovaries of DDT-treated female rats

机译：催眠致毒性治疗雌性大鼠子宫和卵巢中荷尔蒙致癌基因及相关调节微小瘤的表达

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The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-alpha (ER alpha) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest that DDT may also influence expression of microRNAs. However, an impact of DDT on expression of ER, microRNAs, and related target genes has not been fully elucidated. Here, using real-time PCR, we assessed changes in expression of key genes involved in hormonal carcinogenesis as well as potentially related regulatory oncogenic/tumor suppressor microRNAs and their target genes in the uterus and ovaries of female Wistar rats during single and chronic multiple-dose DDT exposure. We found that applying DDT results in altered expression of microRNAs-221, -222, -205, -126a, and -429, their target genes (Pten, Dicer1), as well as genes involved in hormonal carcinogenesis (Esr1, Pgr, Ccnd1, Cyp19a1). Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222, and -205. The data suggest that epigenetic effects induced by DDT as a potential carcinogen may be based on at least two mechanisms: (i) activation of ER alpha followed by altered expression of the target genes encoding receptor Pgr and Ccnd1 as well as impaired expression of Cyp19a1, affecting, thereby, cell hormone balance; and (ii) changed expression of microRNAs resulting in impaired expression of related target genes including reduced level of Cyp19a1 mRNA.
机译：杀虫剂二氯二苯基三氯乙烷（DDT）是能够施加雌激素的异黄素化合物，其产生雌激素受体-α（ERα）的活化，然后改变其下游靶基因的表达。此外，近年来进行的研究表明DDT也可能影响MicroRNA的表达。然而，DDT对ER，MicroRNA和相关靶基因表达的影响尚未完全阐明。在这里，使用实时PCR，我们评估了在单一和慢性多次血清中癌症中涉及激素致癌作用的关键基因表达的变化以及潜在的调节性致癌/肿瘤抑制microRNA和雌性Wistar大鼠卵巢中的靶基因剂量DDT暴露。我们发现施用DDT导致MicroRNA-221，-222,205，-126A和-429的改变表达，其靶基因（PTEN，DICER1）以及参与激素致癌物的基因（ESR1，PGR，CCND1 ，cyp19a1）。值得注意的是，CYP19A1表达似乎也由MicroRNA-221，-222和-205调节。该数据表明，DDT作为潜在致癌物诱导的表观遗传效应可以基于至少两种机制：（i）ERα的激活，然后改变编码受体PGR和CCND1的靶基因的表达以及CYP19A1的表达受损，由此影响细胞激素平衡; （ii）改变了MicroRNA的表达，导致相关靶基因的表达受损，包括CYP19A1 mRNA的降低水平。

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