MicroRNAs and Xenobiotic Toxicity: An Overview

Abstract

The advent of new technologies has paved the rise of various chemicals that are being employed in industrial as well as consumer products. This leads to the accumulation of these xenobiotic compounds in the environment where they pose a serious threat to both target and non-target species. miRNAs are one of the key epigenetic mechanisms that have been associated with toxicity by modulating the gene expression post-transcriptionally. Here, we provide a comprehensive view on miRNA biogenesis, their mechanism of action and, their possible role in xenobiotic toxicity. Further, we review the recent in vitro and in vivo studies involved in xenobiotic exposure induced miRNA alterations and the mRNA-miRNA interactions. Finally, we address the challenges associated with the miRNAs in toxicological studies.

Keywords: ADAMTS9, A disintegrin and metalloproteinase with thrombospondin motifs 9; AHR, Aryl Hydrocarbon Receptor; AMPK, Adenosine Monophosphate-activated protein kinase; ARRB1, Arrestin beta 1; Ag, Silver; Al2O3, Aluminium oxide; Au, Gold; Aβ, Amyloid Beta; BCB, Blood-cerebrospinal fluid barrier; BNIP3−3, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; BaP, Benzo[a]pyrene; Biomarkers; CCNB1, Cyclin B1; CDC25A, M-phase inducer phosphatase 1; CDC25C, M-phase inducer phosphatase 3; CDK, Cyclin-dependent Kinase; CDK1, Cyclin-dependent kinase 1; CDK6, Cyclin-dependent kinase 6; CDKN1b, Cyclin-dependent kinase Inhibitor 1B; CEC, Contaminants of Emerging Concern; COPD, Chronic obstructive pulmonary disease; COX2, Cyclooxygenase-2; CTGF, Connective Tissue Growth Factor; DGCR8, DiGeorge syndrome chromosomal [or critical] region 8; DNA, Deoxy ribonucleic acid; DON, Deoxynivalenol; ER, Endoplasmic Reticulum; Environment; Epigenetics; Fadd, Fas-associated protein with death domain; GTP, Guanosine triphosphate; Gene regulation; Grp78/BIP, Binding immunoglobulin protein; HSPA1A, Heat shock 70 kDa protein 1; Hpf, Hours post fertilization; IL-6, Interleukin 6; IL1R1, Interleukin 1 receptor, type 1; LIN28B, Lin-28 homolog B; LRP-1-, Low density lipoprotein receptor-related protein 1; MAPK, Mitogen Activated Protein Kinase; MC-LR, Microcystin-Leucine Arginine; MC-RR, Microcystin-Arginine Arginine; MRE, MicroRNA Response Elements; Mn, Manganese; NASH, Non-alcoholic steatohepatitis; NET1, Neuroepithelial Cell Transforming 1; NF- ҡB, Nuclear Factor kappa-light-chain-enhancer of activated B cells; NFKBAP, NFKB Activating protein-1; NMDAR, N-methyl-d-aspartate receptor; NPs, Nanoparticles; Non-coding RNAs; Nrf2, Nuclear factor erythroid 2-related factor 2; PDCD4, Programmed cell death protein 4; PFAS, Poly-fluoroalkyl substances; PM2.5, Particulate Matter2.5; RISC, RNA-induced silencing complex; RNA, Ribonucleic acid; RNAi, RNA interference; RNase III, Ribonuclease III; SEMA6D, Semaphorin-6D; SOLiD, Sequencing by Oligonucleotide Ligation and Detection; SPIONs, Superparamagnetic Iron Oxide Nanoparticles; SiO2, Silicon dioxide; TCDD, 2,3,7,8-Tetrachlorodibenzodioxin; TNF-α, Tumor necrosis factor – alpha; TP53, Tumor protein 53; TRBP, Transactivation Response RNA Binding Protein; Toxicity; UTR, Untranslated region; WHO, World Health Organization; Wnt, Wingless-related integration site; ZEA, Zearalanone; Zn, Zinc; bcl2l11, B-cell lymphoma-2-like protein 11; ceRNA, Competing endogenous RNA; lncRNAs, Long non-coding RNA; mRNA, Messenger RNA; miRNA, MicroRNA; qRT-PCR, quantitative Real Time-Polymerase Chain Reaction; ripk 1, Receptor-interacting serine/threonine-protein kinase 1.