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Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene
Environmental Geochemistry and Health ( IF 3.2 ) Pub Date : 2020-10-08 , DOI: 10.1007/s10653-020-00740-x
Mengjie Wang , Jingwen Tan , Chenglan Jiang , Shuting Li , Xinan Wu , Guanghui Ni , Yuefeng He

Arsenic is a wildly distributed carcinogen in the environment. Arsenic-induced apoptosis has been extensively studied in therapeutics and toxicology. LncRNA MEG3 has been extensively studied as apoptosis regulatory gene in recent years. However, it stays unclear regarding how the mechanism of MEG3 regulates arsenic-induced apoptosis. Our focus was to explore the effects of MEG3 on arsenic-induced apoptosis. MTS assay was used to test cell viability, and qRT-PCR was for the examination of gene expressions. The effect of the apoptosis and necrosis after knockdown MEG3 was detected with double staining. Our results demonstrated that MEG3 expression was positively correlated with the concentration of three arsenic species (inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) (p < 0.05). The ability of iAs to induce MEG3 expression was much higher compared with that induced by MMA and DMA. In addition, our experiments confirmed that MEG3 knockdown increased cell viability and arsenic-induced apoptosis, but cell viability decreased after iAs treatment. Moreover, LncRNA MEG3 regulated apoptosis via down-regulate API5 while up-regulate CASP7, CCND3 and APAF1. It is further proved that arsenic-induced apoptosis increased after the knockdown of MEG3, which regulates these genes. These findings provide experimental evidence and possible mechanisms for subsequent research on the effects of arsenic on health.



中文翻译:

无机砷通过调节MEG3基因的表达影响细胞凋亡

砷是环境中分布广泛的致癌物。砷诱导的细胞凋亡已在治疗学和毒理学领域进行了广泛研究。近年来,LncRNA MEG3作为细胞凋亡调节基因已被广泛研究。然而,关于MEG3如何调节砷诱导的细胞凋亡尚不清楚。我们的重点是探讨MEG3对砷诱导的细胞凋亡的影响。MTS测定法用于测试细胞活力,而qRT-PCR用于检查基因表达。用双重染色检测了敲低MEG3后的细胞凋亡和坏死的作用。我们的结果表明,MEG3表达与三种砷(无机砷(iAs),单甲基砷酸(MMA)和二甲基砷酸(DMA))的浓度呈正相关(p <0.05)。iA诱导MEG3表达的能力比MMA和DMA诱导的能力高得多。此外,我们的实验证实,MEG3敲低可提高细胞活力和砷诱导的细胞凋亡,但iAs处理后细胞活力降低。此外,LncRNA MEG3通过下调API5来调节细胞凋亡,而上调CASP7,CCND3和APAF1。进一步证明,在调节这些基因的MEG3敲低后,砷诱导的细胞凋亡增加。这些发现为砷对健康的影响进行后续研究提供了实验证据和可能的机制。

更新日期:2020-10-11
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