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微小 RNA 及其在环境化学致癌中的作用。

MicroRNAs and their role in environmental chemical carcinogenesis.

机构信息

Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, 515041, Guangdong, China.

Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 511486, Guangdong, China.

出版信息

Environ Geochem Health. 2019 Feb;41(1):225-247. doi: 10.1007/s10653-018-0179-8. Epub 2018 Aug 31.

Abstract

MicroRNAs (miRNAs) are a class of small, noncoding RNA species that play crucial roles across many biological processes and in the pathogenesis of major diseases, including cancer. Recent studies suggest that the expression of miRNA is altered by certain environmental chemicals, including metals, organic pollutants, cigarette smoke, pesticides and carcinogenic drugs. In addition, extensive studies have indicated the existence and importance of miRNA in different cancers, suggesting that cancer-related miRNAs could serve as potential markers for chemically induced cancers. The altered expression of miRNA was considered to be a vital pathogenic role in xenobiotic-induced cancer development. However, the significance of miRNA in the etiology of cancer and the exact mechanisms by which environmental factors alter miRNA expression remain relatively unexplored. Hence, understanding the interaction of miRNAs with environmental chemicals will provide important information on mechanisms underlying the pathogenesis of chemically induced cancers, and effectively diagnose and treat human cancers resulting from chronic or acute carcinogen exposure. This study presents the current evidence that the miRNA deregulation induced by various chemical carcinogens, different cancers caused by environmental carcinogens and the potentially related genes in the onset or progression of cancer. For each carcinogen, the specifically expressed miRNA may be considered as the early biomarkers of the cancer process. In this review, we also summarize various target genes of the altered miRNA, oncogenes or anti-oncogenes, and the existing evidence regarding the gene regulation mechanisms of cancer caused by environmentally induced miRNA alteration. The future perspective of miRNA may become attractive targets for the diagnosis and treatment of carcinogen-induced cancer.

摘要

微小 RNA(miRNAs)是一类小的非编码 RNA 分子,在许多生物学过程和重大疾病(包括癌症)的发病机制中发挥着关键作用。最近的研究表明,某些环境化学物质(包括金属、有机污染物、香烟烟雾、农药和致癌药物)会改变 miRNA 的表达。此外,大量研究表明 miRNA 存在于不同的癌症中,并具有重要作用,这表明与癌症相关的 miRNA 可能成为化学诱导癌症的潜在标志物。miRNA 的表达改变被认为是外源性化学物诱导癌症发生的重要致病作用。然而,miRNA 在癌症发病机制中的意义以及环境因素改变 miRNA 表达的确切机制仍相对未知。因此,了解 miRNA 与环境化学物质的相互作用将为化学诱导癌症发病机制提供重要信息,并有效诊断和治疗因慢性或急性致癌物暴露而导致的人类癌症。本研究综述了各种化学致癌剂诱导的 miRNA 失调、环境致癌物引起的不同癌症以及癌症发生或进展中潜在相关基因的现有证据。对于每种致癌剂,特异性表达的 miRNA 可被视为癌症过程的早期生物标志物。在本综述中,我们还总结了改变的 miRNA、癌基因或抑癌基因的各种靶基因,以及关于环境诱导 miRNA 改变引起癌症的基因调控机制的现有证据。miRNA 的未来前景可能成为诊断和治疗致癌物诱导癌症的有吸引力的靶点。

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