Chen Tao
National Center for Toxicological Research, Jefferson, AR, USA.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2010 Apr;28(2):89-124. doi: 10.1080/10590501.2010.481477.
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.
微小RNA(miRNA)是基因表达的重要调节因子。不同致癌物暴露导致的miRNA表达改变已有大量报道。在介绍miRNA的生物合成、调控机制和靶标识别之后,本综述旨在呈现不同生物系统中因不同类型致癌物暴露而失调的miRNA,并讨论它们在化学致癌不同阶段的潜在作用。现有信息表明,大量miRNA的表达会因致癌物暴露而以组织和化学物质特异性的方式轻易改变。致癌剂通常比非致癌化学物质在miRNA表达上诱导更多变化。急性或慢性暴露于致癌物后,癌症靶组织中的变化比非靶组织更多。许多因致癌物而失调的miRNA参与调控对化学致癌各个阶段都很重要的基因,包括外源性物质代谢、致癌物诱导的低甲基化、DNA修复、细胞凋亡、细胞增殖、肿瘤抑制、细胞转化、肿瘤发生、肿瘤血管生成、肿瘤进展、恶性转化及其他功能。许多miRNA发挥着假定的癌基因和肿瘤抑制基因的作用。致癌物的致癌功能可能取决于肿瘤抑制性miRNA和致癌性miRNA之间的平衡。因此,致癌物暴露特有的miRNA谱和miRNA有潜力用作生物标志物,以识别化学物质的遗传毒性和致癌性,并指示致癌物暴露情况。