Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene
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ORIGINAL PAPER
Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene Mengjie Wang . Jingwen Tan . Chenglan Jiang . Shuting Li . Xinan Wu . Guanghui Ni . Yuefeng He
Received: 27 March 2020 / Accepted: 27 September 2020 Ó Springer Nature B.V. 2020
Abstract 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
M. Wang J. Tan C. Jiang S. Li X. Wu Y. He (&) School of Public Health, Kunming Medical University, No.1168 Chunrongxi Road Chenggong District, Kunming, Yunnan Province, China e-mail: [email protected] G. Ni (&) College of Pharmaceutic Science, Yunnan University of Chinese Medicine, No.1076 Yuhua Road Chenggong District, Kunming, Yunnan Province, China e-mail: [email protected]
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. Keywords API5 Apoptosis Arsenic MEG3 DMA MMA
Introduction Maternally expressed (MEG3) is a Long non-coding RNAs (LncRNA) with the length of more than 1.6 kb and has no function of encoding proteins (Yang et al. 2020). MEG3 is recognized as a gene which suppresses tumor. A large number of studies demonstrates that MEG3 regulates the expression of downstream genes such as BCL2, BAX, CASP3, TP53 in several tumors, including glioma, lung cancer, gastric cancer, breast cancer, etc. (Deng et al. 2020; Wu et al. 2018; GhafouriFard et al. 2019) Dong et al. (2018). found that knockdown of MEG3 increases SPHK1 and TGFb1 to inhibit cell apoptosis. A study by Zhang et al. (2019) showed that over-expression of MEG3 increases APAF1 expression and activates CASP9 and CASP3
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Environ Geochem Health
to promote cell apoptosis. It has been suggested that MEG3 exerts
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