Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, The Chinese Academy of Sciences, Donghu South Road 7, Wuhan 430072, People's Republic of China.
Environ Sci Technol. 2012 Jan 3;46(1):34-41. doi: 10.1021/es201514h. Epub 2011 Sep 19.
Studies have demonstrated that microcystins (MCs) can act as potential carcinogens and have caused serious risk to public environmental health. The molecular mechanisms of MC-induced susceptibility to carcinogenesis are largely unknown. In this study, we performed for the first time a comprehensive analysis of changes in microRNAs (miRNAs) and proteins expression in livers of mice treated with MC-LR. Utilizing microarray and two-dimensional gel electrophoresis (2-DE) analysis, we identified 37 miRNAs and 42 proteins significantly altered. Many aberrantly expressed miRNAs were related to various cancers (e.g., miR-125b, hepatocellular carcinoma; miR-21, leukemia; miR-16, chronic lymphocytic leukemia; miR-192, pituitary adenomas; miR-199a-3p, ovarian cancer; miR-34a, pancreatic cancer). Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2) that play crucial roles in liver tumorigenesis were first found to be affected by MC-LR in mouse liver. MC-LR also altered the expression of a number of miRNAs and proteins involved in several pathways related to tumorigenesis, such as glutathione metabolism, VEGF signaling, and MAPK signaling pathway. Integration of post-transcriptomics, proteomics, and transcriptomics reveals that the networks miRNAs and their potential target genes and proteins involved in had a close association with carcinogenesis. These results provide an early molecular mechanism for liver tumorigenesis induced by MCs.
研究表明，微囊藻毒素（MCs）可能作为潜在的致癌物质，对公共环境健康造成严重威胁。MC 诱导致癌易感性的分子机制在很大程度上尚不清楚。在这项研究中，我们首次对 MC-LR 处理的小鼠肝脏中 microRNAs（miRNAs）和蛋白质表达变化进行了全面分析。利用微阵列和二维凝胶电泳（2-DE）分析，我们鉴定出 37 个 miRNAs 和 42 个显著改变的蛋白质。许多异常表达的 miRNAs 与各种癌症有关（例如，miR-125b、肝癌；miR-21、白血病；miR-16、慢性淋巴细胞白血病；miR-192、垂体腺瘤；miR-199a-3p、卵巢癌；miR-34a、胰腺癌）。一些 miRNAs（例如，miR-34a、miR-21）和蛋白质（例如，TGM2、NDRG2）在肝癌发生中起着关键作用，它们首次被发现受到 MC-LR 的影响。MC-LR 还改变了与肿瘤发生相关的几种途径（如谷胱甘肽代谢、VEGF 信号和 MAPK 信号通路）中涉及的许多 miRNAs 和蛋白质的表达。转录组学、蛋白质组学和转录组学的整合表明，miRNAs 及其潜在靶基因和蛋白质参与的网络与致癌作用密切相关。这些结果为 MC 诱导的肝癌发生提供了早期的分子机制。
