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Review
. 2023:96:203-240.
doi: 10.1016/bs.apha.2022.10.002. Epub 2023 Feb 6.

miRNAs and arsenic-induced carcinogenesis

Alexandra N Nail  1 , Ana P Ferragut Cardoso  1 , Lakyn K Montero  1 , J Christopher States  2
Affiliations
Review

miRNAs and arsenic-induced carcinogenesis

Alexandra N Nail et al. Adv Pharmacol. 2023.

Abstract

Arsenic-induced carcinogenesis is a worldwide health problem. Identifying the molecular mechanisms responsible for the induction of arsenic-induced cancers is important for developing treatment strategies. MicroRNA (miRNA) dysregulation is known to affect development and progression of human cancer. Several studies have identified an association between altered miRNA expression in cancers from individuals chronically exposed to arsenic and in cell models for arsenic-induced carcinogenesis. This chapter provides a comprehensive review for miRNA dysregulation in arsenic-induced cancer.

Keywords: Arsenic; Bladder; Cancer; Chronic; Kidney; Lung; Prostate; Skin; miRNA.

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Conflict of interest statement

Conflict of interest statement The authors declare they have no financial conflicts of interest other than grants R01ES02778, R21ES030334, P30ES030283, T32ES011564 and R25CA134283 that supported the authors.

Figures

Fig. 1
Fig. 1
Metabolism and toxicity of arsenic metabolites. (A) Arsenic is predominantly present in the environment as either arsenate or arsenite. Presented is the classical metabolic pathway of arsenic (As) in humans (Thomas, 2016). In liver, arsenate is first reduced to arsenite. Arsenite is then methylated by Arsenic III methyltransferase (AS3MT) producing methylarsonate (MMAV). MMAV is then reduced to methylarsonous acid (MMAIII). MMAIII is methylated by AS3MT to form dimethylarsinous acid (DMAV) which is then reduced to form DMAIII. (B) Toxicity of arsenic metabolites. Trivalent methylated arsenic species are highly cytotoxic and genotoxic compared to arsenite and pentavalent arsenicals.
Fig. 2
Fig. 2
Schematic overview of canonical miRNA biosynthesis. Primary miRNA transcript (pri-miRNA) is transcribed by RNA polymerase II and processed in the nucleus by DROSHA/DGCR8 into pre-miRNAs. Pre-miRNAs are exported to the cytoplasm via Exportin 5 (XPO5), followed by subsequent Dicer cleavage to its mature length. The guide miRNA strand is loaded together with Argonaute (AGO) proteins into the RNA-induced silencing complex (RISC) where it guides RISC to target and silence mRNAs via mRNA cleavage, translational repression, or deadenylation.
Fig. 3
Fig. 3
Differential expression of miRNAs dysregulated across arsenic transformed cell models and arsenic-induced human cancer. (A) miRNAs dysregulated across different cell models representing four target tissues of arsenic-induced cancer (Skin, Lung, Prostate, Bladder). (B) miRNAs dysregulated between arsenic transformed cell models (Skin, Lung, Prostate) and arsenic-induced human cancers (Humans). Induced miRNAs are represented in black, suppressed miRNAs are represented in light gray, ambiguous changes in expression (conflicting results between studies) are represented in dark gray, and miRNAs not examined or that were not found to be significantly different in a particular cell model or tumor are represented as white.
See this image and copyright information in PMC

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