title: Genomic profiling of microRNAs and proteomics reveals an early molecular alteration associated with tumorigenesis induced by MC-LR in mice.
abstract: 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.
authors: 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.
authors: Yanyan
authors: Y
authors: Zhao
authors: Ping
authors: P
authors: Xie
authors: Huihui
authors: H
authors: Fan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008387:Marine Toxins; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D052998:Microcystins / Q000633:toxicity*; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D008387:Marine Toxins; D035683:MicroRNAs; D052998:Microcystins; C057862:cyanoginosin LR