Cooperation between NRF2-mediated transcription and MDIG-dependent epigenetic modifications in arsenic-induced carcinogenesis and cancer stem cells

Bi, Zhuoyue; Zhang, Qian; Fu, Yao; Seno, Akimasa; Wadgaonkar, Priya; Qiu, Yiran; Almutairy, Bandar; Xu, Liping; Zhang, Wenxuan; Thakur, Chitra; Chen, Fei

doi:10.1016/j.semcancer.2021.03.030

Cited by 14 publications

(13 citation statements)

References 73 publications

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“…Fetal arsenic exposure can also increase the effects of skin carcinogens (topical 12-O-tetradecanoyl phorbol-13-acetate, TPA) in mice by elevating the levels of CD34+ cells and expression of RAC1 (involved in self-renewal stimulation; Waalkes et al, 2008 ). Bronchial epithelial cells exposed to arsenic, acquired CSC-like features such as asymmetric division, self-renewal, and increased expression of stemness genes ( Chang et al, 2020 ; Bi et al, 2021 ).…”

Section: Genetic and Epigenetic Effects Associated With Arsenic Exposurementioning

confidence: 99%

“…Fetal arsenic exposure can also increase the effects of skin carcinogens (topical 12-O-tetradecanoyl phorbol-13acetate, TPA) in mice by elevating the levels of CD34+ cells and expression of RAC1 (involved in self-renewal stimulation; Waalkes et al, 2008). Bronchial epithelial cells exposed to arsenic, acquired CSC-like features such as asymmetric division, • Elevated levels of H3K9me2 within promoter regions of genes involved in the Base excision repair (BER) pathway (MPG, XRCC1, and PARP1) Barchowsky et al, 1999;Smith et al, 2001;Chakraborty and De, 2009;Cooper et al, 2009;Kitchin and Conolly, 2010;Martinez et al, 2010;Smeester et al, 2011;Roy et al, 2016;Smeester and Fry, 2018;Ding et al, 2021 Interference with DNA repair • Hypomethylation in D-loop and ND6 gene along with increased expression of ND4, ND6, mtTfam, and higher mtDNA copy number Sanyal et al, 2018;Cheikhi et al, 2020 self-renewal, and increased expression of stemness genes (Chang et al, 2020;Bi et al, 2021). Arsenic-mediated malignant transformation has been linked to disruption of the KRAS gene.…”

Section: Genetic Effectsmentioning

confidence: 99%

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Health Effects Associated With Pre- and Perinatal Exposure to Arsenic

Martínez

Lam²

2021

Front. Genet.

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Inorganic arsenic is a well-established human carcinogen, able to induce genetic and epigenetic alterations. More than 200 million people worldwide are exposed to arsenic concentrations in drinking water exceeding the recommended WHO threshold (10μg/l). Additionally, chronic exposure to levels below this threshold is known to result in long-term health effects in humans. The arsenic-related health effects in humans are associated with its biotransformation process, whereby the resulting metabolites can induce molecular damage that accumulates over time. The effects derived from these alterations include genomic instability associated with oxidative damage, alteration of gene expression (including coding and non-coding RNAs), global and localized epigenetic reprogramming, and histone posttranslational modifications. These alterations directly affect molecular pathways involved in the onset and progression of many conditions that can arise even decades after the exposure occurs. Importantly, arsenic metabolites generated during its biotransformation can also pass through the placental barrier, resulting in fetal exposure to this carcinogen at similar levels to those of the mother. As such, more immediate effects of the arsenic-induced molecular damage can be observed as detrimental effects on fetal development, pregnancy, and birth outcomes. In this review, we focus on the genetic and epigenetic damage associated with exposure to low levels of arsenic, particularly those affecting early developmental stages. We also present how these alterations occurring during early life can impact the development of certain diseases in adult life.

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Section: Genetic and Epigenetic Effects Associated With Arsenic Exposurementioning

confidence: 99%

Section: Genetic Effectsmentioning

confidence: 99%

Health Effects Associated With Pre- and Perinatal Exposure to Arsenic

Martínez

Lam²

2021

Front. Genet.

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“…In our recent RNA-seq analysis for the WT and Nrf2 KO cells, we noted a marginal transcription of the exon 1 of this transcript (bottom panel of Figure 7 ), indicating a limited degree of expression of this transcript. Since the identification of Nrf2 gene and its encoded Nrf2 protein, a number of antibodies had been developed that can detect Nrf2 proteins with a molecular weight (MW) ranged from 65 to 110 kDa [ 43 ]. Based on the amino acid sequence, the predicted MW of Nrf2 is 66 kDa.…”

Section: Some Ambiguities On the Molecular Characteristics Of Nrf2 Proteinmentioning

confidence: 99%

“…The specificity of antibodies that are widely used currently to examine the level of Nrf2 protein in Western blotting is another topic that has been extensively discussed thus far [ 43 ]. Lau and colleagues [ 44 ] tested anti-Nrf2 antibodies from three different commercial sources and found that one antibody detected a predominant Nrf2 band with a MW of 110 kDa, and concluded that the authentic Nrf2 protein in immunoblotting should be the band at a migrating position around 110 kDa.…”

Section: Some Ambiguities On the Molecular Characteristics Of Nrf2 Proteinmentioning

confidence: 99%

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New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis

Wadgaonkar

et al. 2021

Antioxidants

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Environment exposure to arsenic had been linked to increased incidents of human cancers. In cellular and animal experimental systems, arsenic has been shown to be highly capable of activating several signaling pathways that play critical roles in cell growth regulation, malignant transformation and the stemness of cancer stem-like cells. Emerging evidence indicates certain oncogenic properties of the Nrf2 transcription factor that can be activated by arsenic and many other environmental hazards. In human bronchial epithelial cells, our most recent data suggested that arsenic-activated Nrf2 signaling fosters metabolic reprogramming of the cells through shifting mitochondrial TCA cycle to cytosolic glycolysis, and some of the metabolites in glycolysis shunt the hexosamine biosynthesis and serine-glycine pathways important for the energy metabolism of the cancer cells. In the current report, we further demonstrated direct regulation of oncogenic signals by arsenic-activated Nrf2 and connection of Nrf2 with ATF3 stress transcription factor. Meanwhile, we also highlighted some unanswered questions on the molecular characteristics of the Nrf2 protein, which warrants further collaborative efforts among scientists for understanding the important role of Nrf2 in human cancers either associated or not to environmental arsenic exposure.

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