Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene

Wang, Mengjie; Tan, Jingwen; Jiang, Chaowei; Li, Shu-Ting; Wu, Xinan; Ni, Guanghui; He, Yuefeng

doi:10.1007/s10653-020-00740-x

Cited by 10 publications

(6 citation statements)

References 37 publications

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“…Therefore, various arsenic species have different biological effects and genotoxicities. For example, the mRNA expression levels of LincRNA‐p21, 33 HOTAIR, 33 and MEG3 24 induced by NaAsO 2 was higher than those induced by MMA and DMA. To elucidate the relationship between the speciation of arsenic and AS3MT expression, we examined the effects of arsenic speciation on AS3MT expression by Western blot in the A549 and 16HBE cells.…”

Section: Discussionmentioning

confidence: 94%

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Involvement of a AS3MT/c‐Fos/p53 signaling axis in arsenic‐induced tumor in human lung cells

Sun

Cheng

Tang

et al. 2022

Environmental Toxicology

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Arsenite methyltransferase (AS3MT) is an enzyme that catalyzes the dimethylation of arsenite (+3 oxidation state). At present, the studies on arsenic carcinogenicity mainly focus on studying the polymorphisms of AS3MT and measuring their catalytic activities.We recently showed that AS3MT was overexpressed in lung cancer patients who had not been exposed to arsenic. However, little is known about the molecular mechanisms of AS3MT in arsenite-induced tumorigenesis. In this study, we showed that AS3MT protein expression was higher in the arsenic-exposed population compared to the unexposed population. AS3MT was also overexpressed in human lung adenocarcinoma (A549) and human bronchial epithelial (16HBE) cells exposed to arsenic (A549: 20-60 μmol/L; 16HBE: 2-6 μmol/L) for 48 h. Furthermore, we investigated the effects of AS3MT on cell proliferation and apoptosis using siRNA. The downregulation of AS3MT inhibited the proliferation and promoted the apoptosis of cells. Mechanistically, AS3MT was found to specifically bind to c-Fos, thereby inhibiting the binding of c-Fos to c-Jun.Additionally, the siRNA-mediated knockdown of AS3MT enhanced the phosphorylation of Ser392 in p53 by upregulating p38 MAPK expression. This led to the activation of p53 signaling and the upregulated expression of downstream targets, such as p21, Fas, PUMA, and Bax. Together, these studies revealed that the inorganic arsenic-mediated upregulation of AS3MT expression directly affected the proliferation and apoptosis of cells, leading to arsenic-induced toxicity or carcinogenicity.

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Section: Discussionmentioning

confidence: 94%

“…The % MMA was equal to the MMA/tAs, and the % DMA was equal to DMA/tAs. In addition, the primary methylation index (PMI) was equal to the (MMA + DMA)/tAs, and the secondary methylation index (SMI) was equal to the DMA/(MMA + DMA) 24 …”

Section: Methodsmentioning

confidence: 99%

Involvement of a AS3MT/c‐Fos/p53 signaling axis in arsenic‐induced tumor in human lung cells

Sun

Cheng

Tang

et al. 2022

Environmental Toxicology

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“…After exposure, snakehead rhabdovirus was used to infect the zebrafish, and analysis of their immune reactions showed impaired innate immune function [9]. Other studies have suggested that As poisoning may affect T cell differentiation [25,26] and cell apoptosis [27,28]. However, little research has been conducted on the effect of As on eosinophil count.…”

Section: Discussionmentioning

confidence: 99%

Associations and Interactions between Heavy Metals with White Blood Cell and Eosinophil Count

Huang¹,

Hsieh²,

Wang³

et al. 2022

Int. J. Med. Sci.

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The accumulation of heavy metals in the body has been associated with an elevated immune response. The aim of this study was to investigate the associations among heavy metals and white blood cell (WBC) and eosinophil count in the general population in southern Taiwan. We also explored the interactions and synergetic effects of heavy metals on WBC and eosinophil count. We conducted a health survey in the general population living in southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb), and urine cadmium (Cd), copper (Cu), nickel, arsenic (As), chromium and manganese (Mn). A total of 2,447 participants were enrolled. In multivariable analysis, high concentrations of Pb (log per 1 mg/L; coefficient β, 0.332; p = 0.005) and Cu (log per 1 µg/dL; coefficient β, 0.476; p < 0.001) were significantly associated with a high WBC count. In addition, high concentrations of Pb (log per 1 mg/L; coefficient β, 0.732; p < 0.001), As (log per 1 µg/L; coefficient β, 0.133; p = 0.015), Cu (log per 1 µg/dL; coefficient β, 0.181; p = 0.018), and Cd (log per 1 µg/L; coefficient β, 0.139; p = 0.002) were significantly associated with a high eosinophil count. Further, the effect of interactions between Pb and As (coefficient β, 0.721; p = 0.029) and Mn and Cu (coefficient β, 0.482; p = 0.018) on WBC count, and As and Cu (unstandardized coefficient β, 0.558; p = 0.002) on eosinophil count were statistically significant. In conclusion, the heavy metals Pb, As, Cu, and Cd were associated with WBC and eosinophil count. In addition, synergistic effects of heavy metal poisoning on the association with WBC and eosinophil count were also observed.

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“…It has been reported that paternal non-occupational exposure to environmental arsenic elevated DNA methylation levels of MEG3 in the sperm of 353 male subjects [ 87 ]. The results from a case-control study revealed that MEG3 levels in peripheral blood lymphocytes were positively correlated with the levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the urine of workers exposed to arsenic [ 88 ]. It has also been reported that MEG3 levels in peripheral blood were reduced in workers exposed to arsenic occupationally, while the arsenic concentrations were increased in the urine [ 89 ].…”

Section: Meg3 In Carcinogenesis Of Heavy Metalsmentioning

confidence: 99%

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

Zhang

Shi

et al. 2023

Toxics

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Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.

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Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene

Cited by 10 publications

References 37 publications

Involvement of a AS3MT/c‐Fos/p53 signaling axis in arsenic‐induced tumor in human lung cells

Involvement of a AS3MT/c‐Fos/p53 signaling axis in arsenic‐induced tumor in human lung cells

Associations and Interactions between Heavy Metals with White Blood Cell and Eosinophil Count

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

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