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Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea

ABSTRACT: Dysregulated expression of microRNA (miRNA) has been extensively detected in human cancer tissues and has shown promise in defining tumor status. It, however, is little known whether and when expression of miRNAs can be changed in normal tissues after carcinogen exposure. To explore possible time-course changes of miRNA expression induced by carcinogens, we treated mice with one dose of 120 mg/kg body weight model genotoxic carcinogen N-ethyl-N-nitrosourea (ENU) and vehicle control. The miRNA expression profiles were determined in the mouse livers in a time-course manner. MiRNAs were isolated from the livers of ENU-treated and control mice at days 1, 3, 7, 15, 30 and 120 after the treatment. The miRNA expressions were determined using RT2-mouse miRNA PCR Array. Principal component analysis of the gene expression profiles showed that miRNA expression at post-treatment days 7 and 15 were different from those at the other time points and the controls. The numbers of the dysregulated miRNAs changed with time, being 3, 5, 14, 32, 5 and 5 at post-treatment days 1, 3, 7, 15, 30 and 120, respectively. Functional analysis of the differentially expressed miRNA at post-treatment days 7 and 15 indicated that the major functions of these ENU-induced dysregulated miRNAs were mainly associated with DNA repair and tumorigenesis, suggesting the microRNA expression is related to genotoxicity of ENU. These results propose that one to two weeks after ENU exposure is the best time for miRNA expression sampling; and that a large number of miRNAs whose expression is dysregulated after carcinogen exposure could be an indicator for carcinogenic damage. Series type: Non-coding RNA profiling by RT-PCR

ORGANISM(S): Mus musculus

PROVIDER: GSE20248 | GEO | 2010/11/04

SECONDARY ACCESSION(S): PRJNA124213

REPOSITORIES: GEO

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Project description:Background: Histomonas meleagridis is an anaerobic, intercellular parasite, which infects gallinaceous birds such as turkeys and chickens. In recent years, the reemergence of Histomoniasis has caused serious economic losses as drugs to treat the disease have been banned. At present, research of H. meleagridis focuses on virulence, gene expression analysis, and the innate immunity of the host. However, there are no study on the differentially expressed miRNAs (DEMs) associated with the liver induced by H. meleagridis. In this research, high-throughput sequencing was used to analyze the expression profile of liver miRNA at 10 and 15 days post-infection (DPI) in chickens infected with Chinese JSYZ-F strain H. meleagridis. Results: Compared with the uninfected control, 120 and 118 DEMs were found in the liver of infected chickens at 10 DPI and 15 DPI, respectively, of which 74 DEMs were shared at two-time points. Differentially expressed miRNAs were classified into three types according to the time of infection: L1, 45 miRNAs differentially expressed only at 10 DPI, were predicted to target 1646 genes; L2, 43 miRNAs differentially expressed only at 15 DPI, were predicted to target 2257 genes; L3, 75 miRNAs differentially expressed at both 10 DPI and 15 DPI, were predicted to target 1623 genes. A total of 89, 87 and 41 significantly enriched GO terms (p<0.05) were identified at L1, L2 and L3, respectively. The KEGG pathway analysis of differentially expressed miRNA target genes were shown that 3, 4 and 5 significantly enriched KEGG pathway (p<0.05) were identified at L1, L2 and L3, respectively. Conclusion: This article suggested that liver miRNA expression was dynamically altered by H. meleagridis and host and showed that the expression pattern of the L1 class DEMs were more favourable for controlling the development of the inflammatory response, whereas the L2 class DEMs were more favourable for enhancing the inflammatory response. Inflammation-associated miRNA expression patterns were consistent with the liver inflammatory process after artificial infection. The results of the study laid the foundation for an in-depth analysis of the pathogenic mechanism of H. meleagridis from the perspective of host miRNAs.

Project description:Purpose: To study the differential expression of microRNA (miRNA) profiles between intraocular medulloepithelioma (ME) and normal control tissue. Material and methods: Total RNA was extracted from formalin fixed paraffin-embedded intraocular ME (n=7) and from age matched ciliary body controls (n=8). The clinical history and phenotype was recorded. MiRNA profiles were determined using the Affymetrix® GeneChip® miRNA Arrays analyzed using expression console 1.3 software. Validation of significantly dysregulated miRNA was confimed by quantitaive real-time PCR. The web-based DNA Intelligent Analysis (DIANA)-miRPath v2.0 was used to perform enrichment analysis of differentially expressed (DE) miRNA gene targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results: The pathologic evaluation revealed one benign and six malignant tumors (malignant teratoid, n=2; malignant non-teratoid, n= 4; benign non-teratoid, n=1). A total of 88 miRNAs were upregulated and 43 miRNAs were down regulated significantly in the tumor specimens (P<0.05). Many of these significantly dysregulated miRNAs were known to play various roles in carcinogenesis and tumor behavior. RT-PCR validated three significantly upregulated miRNAs and three significantly down regulated miRNAs namely miR-217,miR-216a,miR-216b,miR-146a.miR-509-3p and miR-211. 56 miRNAs were significantly dysregulated in teratoid versus non-teratoid malignant tumors. Many DE miRNAs that were significant in ME tumors showed dysregulation in retinoblastoma, and glioblastoma. Several miRNAs in teratoid tumors were significantly up-regulated as in precursor, normal and reactive human cartilage. Enriched pathway analysis suggested a significant association of upregulated miRNAs with 15 pathways involved in prion disease and several types of cancer. The pathways involving significantly down-regulated miRNAs included the toll-like receptor (p<4.36E-16) and NF-kappa B signaling pathways (p<9.00E-06). Conclusions: We report significantly dysregulated miRNAs in intraocular ME tumors, which exhibited abnormal profiles in other cancers as well such as retinoblastoma and glioblastoma. Pathway analysis of all dysregulated miRNAs shared commonalities with other cancer pathways.

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Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea

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