砷暴露人群相关LncRNAs在肿瘤形成中的作用研究进展
Research progress on role of LncRNAs in tumorigenesis in arsenic-exposed population
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摘要:
无机砷是一种广泛的环境有毒物质，已被国际癌症研究机构确认为人类致癌物，可通过多种途径进入机体，增加肺癌、乳腺癌、膀胱癌等肿瘤发生风险，但其机制研究仍难以突破。研究者从多方面对砷的遗传毒性和致癌机制进行了探讨，发现职业砷接触代谢活跃人群相关长链非编码RNA(LncRNAs)表达显著改变，提示存在肿瘤启动危险因素。该文主要综述了不同砷甲基化代谢模式及其代谢产物含量和比例，及其诱导LncRNAs异常表达在肿瘤中的作用。砷暴露人群相关LncRNAs作为原癌基因(MALAT1、HOTAIR)通过协调低氧诱导因子、转录因子NF-E2相关因子2(Nrf2)信号通路等促进肿瘤启动，作为抑癌基因(MEG3、LincRNA-p21)在抑制肿瘤细胞增殖和侵袭中发挥作用，LncRNAs也参与竞争性内源RNA或p53网络协同调控肿瘤发生发展。本文旨在为砷暴露高危人群筛查和相关疾病早诊早治提供新思路。
Abstract: Inorganic arsenic (iAs) is a widespread environmental toxicant that has been classified as a human carcinogen by the International Agency for Research on Cancer. It is associated with increased risks of bladder, lung, and breast cancer via a variety of ways. How arsenic exposure promotes diseases remains unclear. Researchers have explored the genotoxicity and carcinogenic mechanisms of arsenic from many aspects, and have found significant changes in the expression of long non-coding RNAs (LncRNAs) in occupational arsenic-exposed population, indicating potential risk for cancer initiation. This article reviewed various metabolic patterns of arsenic methylation and associated contents and proportions of its metabolites, as well as the role of abnormal expression of LncRNAs induced by arsenic in tumors. LncRNAs as proto-oncogenes (MALAT1 and HOTAIR for example) in arsenic-exposed population can promote tumor initiation by coordinating hypoxia inducible factors and transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway; as antioncogenes (MEG3 and LincRNA-p21 for example) they can inhibit the proliferation and invasion of cancer cells; they also participate in the co-regulation of tumorigenesis with competing endogenous RNA or p53 network. The article aimed to provide new ideas for screening high-risk population with arsenic exposure and for the early diagnosis and treatment of related diseases.
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