Arsenic exposure triggers a shift in microRNA expression

Sturchio, Elena; Colombo, Teresa; Boccia, Priscilla; Carucci, Nicoletta; Meconi, Claudia; Minoia, Claudio; Macino, Giuseppe

doi:10.1016/j.scitotenv.2013.11.092

Cited by 48 publications

(29 citation statements)

References 36 publications

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“…They regulate gene expression by acting as oncogenes or tumor suppressors, thereby impacting cell proliferation, carcinogenesis, or apoptosis. They function by interacting with target mRNA, suppressing mRNA level and repressing protein translation . The role of miRNAs on i As‐induced toxicity in Jurkat T cells was examined by applying transcriptomics and bioinformatics tools to reconstruct arsenic‐relevant molecular pathways and miRNA regulatory networks .…”

Section: Mechanisms Involved In Arsenic Tumorigenesismentioning

confidence: 99%

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

Tchounwou

Yedjou

Udensi

et al. 2018

Environmental Toxicology

134

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Human exposure to inorganic arsenic (iAs) is a global health issue. Although there is strong evidence for iAs-induced toxicity at higher levels of exposure, many epidemiological studies evaluating its effects at low exposure levels have reported mixed results. We comprehensively reviewed the literature and evaluated the scientific knowledge on human exposure to arsenic, mechanisms of action, systemic and carcinogenic effects, risk characterization, and regulatory guidelines. We identified areas where additional research is needed. These priority areas include: (1) further development of animal models of iAs carcinogenicity to identify molecular events involved in iAs carcinogenicity; (2) characterization of underlying mechanisms of iAs toxicity; (3) assessment of genderspecific susceptibilities and other factors that modulate arsenic metabolism; (4) sufficiently powered epidemiological studies to ascertain relationship between iAs exposure and reproductive/ developmental effects; (5) evaluation of genetic/epigenetic determinants of iAs effects in children;and (6) epidemiological studies of people chronically exposed to low iAs concentrations.

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Section: Mechanisms Involved In Arsenic Tumorigenesismentioning

confidence: 99%

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

Tchounwou

Yedjou

Udensi

et al. 2018

Environmental Toxicology

134

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“…Arsenic exposure has also been linked to altered histone modifications in vitro and in circulating leukocytes collected from humans with chronic arsenic exposure through drinking water (Jo et al ., 2009; Zhao et al ., 2010; Chu et al ., 2011; Ge et al ., 2013). While it has been proposed that arsenic can also modify microRNA (miRNA) expression and thus altering gene expression (Ren et al ., 2011; Li et al ., 2012; Martinez-Pacheco et al ., 2014), this has only been studied in vitro (Sturchio et al ., 2012; Rager et al ., 2013; Sturchio et al ., 2014). To our knowledge, there remains a lack of information regarding the effects of chronic arsenic exposure on miRNA expression in vivo .…”

Section: Introductionmentioning

confidence: 99%

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Ren

Gaile

Gong

et al. 2015

Toxicology and Applied Pharmacology

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Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (P-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate-cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g. miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress.

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“…In addition to the commonly studied epigenetic alterations such as DNA methylation and histone post-translational modifications, miRNA-mediated silencing also plays an important role in arsenic-induced carcinogenesis. 44 Defects in the proper regulation of epigenetic marks can lead to inappropriate activation or suppression of critical oncogenes or tumor suppressor genes, which can lead to cancer development. 59,60 The expression of SATB2 is often found disrupted in various types of cancers including lung, breast, colon, and ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

“…42 Several studies have reported that arsenic exposure causes changes in miRNA expression. [43][44][45][46] Examples of arsenic-deregulated miRNAs include miR-29, -183, -192, etc. 45,46 Here we report for the first time that arsenic is able to trigger the down-regulation of miR-31, a known negative regulator of SATB2.…”

mentioning

confidence: 99%

Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation

Chen

Sun

et al. 2018

Molecular Carcinogenesis

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Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.

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Arsenic exposure triggers a shift in microRNA expression

Cited by 48 publications

References 36 publications

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation

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