The role of MicroRNA in chemical carcinogenesis.
MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens.
Chen
Tao
T
National Center for Toxicological Research, Jefferson, AR, USA. tao.chen@fda.hhs.gov <tao.chen@fda.hhs.gov>
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics
D002273:Carcinogens; D035683:MicroRNAs; D009153:Mutagens