Oxidative Stress, Epigenetics, and Cancer Stem Cells in Arsenic Carcinogenesis and Prevention

Li, Lingzhi; Chen, Fei

doi:10.1007/s40495-016-0049-y

Cited by 40 publications

(21 citation statements)

References 71 publications

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“…Eukaryotic cells experience various types of stress under physiological and pathological conditions, such as oxidative stress, heat shock, endoplasmic reticulum stress, etc. 1 , 2 . Cellular stress has been implicated in aging 3 and various diseases, including cancer 4 , 5 , cardiac conditions 6 , 7 , and neurological disorders 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation

et al. 2018

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Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3′UTR lengths, production of which is influenced by cellular conditions. Here, we show that arsenic stress elicits global shortening of 3′UTRs through preferential usage of proximal polyadenylation sites during stress and enhanced degradation of long 3′UTR isoforms during recovery. We demonstrate that RNA-binding protein TIA1 preferentially interacts with alternative 3′UTR sequences through U-rich motifs, correlating with stress granule association and mRNA decay of long 3′UTR isoforms. By contrast, genes with shortened 3′UTRs due to stress-induced APA can evade mRNA clearance and maintain transcript abundance post stress. Furthermore, we show that stress causes distinct 3′UTR size changes in proliferating and differentiated cells, highlighting its context-specific impacts on the 3′UTR landscape. Together, our data reveal a global, 3′UTR-based mRNA stability control in stressed cells and indicate that APA can function as an adaptive mechanism to preserve mRNAs in response to stress.

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Section: Introductionmentioning

confidence: 99%

Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation

et al. 2018

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“…Interestingly, many of the studies investigating the pathogenic effects of arsenic exposure use concentrations of arsenite in the >5 µM micromolar range [375–750 ppb As(III)], reflecting concentrations that might be observed only in the most severely affected areas. Many of the observed effects in this range, such as increased reactive oxygen species (ROS) production (Alarifi et al ., 2013; Jiang et al ., 2013; Kumar et al ., 2014), DNA damage (Andrew et al ., 2006; Hughes et al ., 2011; Prakash et al ., 2016), mitochondrial dysfunction (Liu et al ., 2005), glutathione depletion (Li and Chen, 2016), and protein modifications (Shen et al ., 2013), might not occur at lower, more relevant concentrations. Furthermore, the compound, cell type, and time of treatment matters, with As 2 O 3 exhibiting a more consistent increase in ROS production at acute time points (Barchowsky et al ., 1999; Yen et al ., 2012; Lu et al ., 2014), whereas chronic NaAsO 2 treatment (i.e.…”

Section: Introductionmentioning

confidence: 99%

Low-level arsenic causes proteotoxic stress and not oxidative stress

Dodson

Vega

Harder

et al. 2018

Toxicology and Applied Pharmacology

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Prolonged exposure to arsenic has been shown to increase the risk of developing a number of diseases, including cancer and type II diabetes. Arsenic is present throughout the environment in its inorganic forms, and the level of exposure varies greatly by geographical location. The current recommended maximum level of arsenic exposure by the EPA is 10μg/L, but levels>50-1000μg/L have been detected in some parts of Asia, the Middle East, and the Southwestern United States. One of the most important steps in developing treatment options for arsenic-linked pathologies is to understand the cellular pathways affected by low levels of arsenic. Here, we show that acute exposure to non-lethal, low-level arsenite, an environmentally relevant arsenical, inhibits the autophagy pathway. Furthermore, arsenite-induced autophagy inhibition initiates a transient, but moderate ER stress response. Significantly, low-level arsenite exposure does not exhibit an increase in oxidative stress. These findings indicate that compromised autophagy, and not enhanced oxidative stress occurs early during arsenite exposure, and that restoring the autophagy pathway and proper proteostasis could be a viable option for treating arsenic-linked diseases. As such, our study challenges the existing paradigm that oxidative stress is the main underlying cause of pathologies associated with environmental arsenic exposure.

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“…An imbalance in the production and removal of ROS can be directly or indirectly involved in the initiation, promotion, and progression of carcinogenesis (Schumacker, ). ROS may damage DNA and chromosomes, induce epigenetic alterations in DNA or histones, interact with oncogenes or tumor suppressor genes, and change immunological mechanisms (Afanas'ev, ; Mikhed et al, ; Li and Chen, ). A few epidemiologic studies have examined the role of oxidative stress in colorectal carcinogenesis.…”

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confidence: 99%

Cytoplasmic Localization of RUNX3 via Histone Deacetylase‐Mediated SRC Expression in Oxidative‐Stressed Colon Cancer Cells

Kang

Piao

Ryu

et al. 2017

Journal Cellular Physiology

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Runt domain transcription factor 3 (RUNX3) is a transcription factor that functions as a tumor suppressor. RUNX3 is frequently inactivated by epigenetic silencing or its protein mislocalization (cytoplasmic localization) in many cancer types. This study investigated whether oxidative stress induces redistribution of RUNX3 from the nucleus to the cytoplasm. The cytoplasmic localization of RUNX3 was associated with oxidative stress-induced RUNX3 phosphorylation at tyrosine residues via SRC activation. Moreover, oxidative stress increased expression of histone deacetylases (HDACs). RUNX3 phosphorylation and SRC expression induced by oxidative stress were inhibited by knockdown of HDAC1, restoring the nuclear localization of RUNX3 under oxidative stress. In conclusion, these results demonstrate that HDAC1- and SRC-mediated phosphorylation of RUNX3 induced by oxidative stress is associated with the cytoplasmic localization of RUNX3 and can lead to RUNX3 inactivation and carcinogenesis. J. Cell. Physiol. 232: 1914-1921, 2017. © 2016 Wiley Periodicals, Inc.

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Oxidative Stress, Epigenetics, and Cancer Stem Cells in Arsenic Carcinogenesis and Prevention

Cited by 40 publications

References 71 publications

Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation

Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation

Low-level arsenic causes proteotoxic stress and not oxidative stress

Cytoplasmic Localization of RUNX3 via Histone Deacetylase‐Mediated SRC Expression in Oxidative‐Stressed Colon Cancer Cells

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