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Triazophos-induced toxicity in zebrafish: miRNA-217 inhibits nup43

机译:三唑磷诱导的斑马鱼毒性:miRNA-217抑制nup43

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摘要

Triazophos is a highly toxic organophosphorus pesticide, causing acute toxicity to brain tissue, and neurotoxicity and embryotoxicity to animals. Therefore, triazophos is considered as a public health problem due to its acute hazard index. MicroRNAs (miRNAs), a class of endogenous noncoding RNAs, can regulate the expression of target gene(s) by mediating mRNA cleavage or translational repression in organisms exposed to environmental chemicals. We found that nup43 is targeted by miR-217, which was significantly regulated in adult zebrafish (Danio rerio) exposed to triazophos (phenyl-1,2,4-triazolyl-3-(o,o-diethyl thionophosphate)). The expression of nup43 in both mRNA and protein levels was downregulated in a dose-dependent manner upon stimulation with triazophos. A dual luciferase reporter assay demonstrated that miR-217 interacted with the 3′-untranslated regions (3′-UTR) of nup43. The expression of nup43 in both mRNA and protein level was reduced in ZF4 cells when transfected with an miR-217 mimic, but increased when transfected with an miR-217 inhibitor. As a result, nup43 is targeted by miR-217 upon triazophos exposure. We suggest that miR-217 could be a potential toxicological biomarker for triazophos.
机译:三唑磷是一种剧毒的有机磷农药,对脑组织有急性毒性,对动物有神经毒性和胚胎毒性。因此,三唑磷由于其急性危害指数而被认为是公共卫生问题。 MicroRNA(miRNA)是一类内源性非编码RNA,可以通过介导暴露于环境化学物质的生物体中的mRNA裂解或翻译抑制来调节靶基因的表达。我们发现,nup43受到miR-217的靶向,miR-217在暴露于三唑磷(苯基-1,2,4-三唑基-3-(邻,邻-二乙基硫代磷酸酯))的成年斑马鱼(达尼奥里奥)中受到显着调节。在三唑磷刺激下,nup43在mRNA和蛋白质水平中的表达均以剂量依赖性方式下调。双重荧光素酶报告基因测定表明,miR-217与nup43的3'-非翻译区(3'-UTR)相互作用。当用miR-217模拟物转染时,ZF4细胞中nup43的mRNA和蛋白质水平表达均降低,但当转染miR-217抑制剂时,nup43的表达增加。结果,三唑磷暴露后,miR-217靶向nup43。我们建议miR-217可能是三唑磷的潜在毒理学生物标志物。

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