Absence of mature microRNAs inactivates the response of gene expression to carcinogenesis induced by N-ethyl-N-nitrosourea in mouse liver
文献类型:期刊论文
作者 | Luan, Yang1; Qi, Xinming2![]() ![]() |
刊名 | JOURNAL OF APPLIED TOXICOLOGY
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出版日期 | 2014-12 |
卷号 | 34期号:12页码:1409-1417 |
关键词 | microRNAs gene expression microarray carcinogenesis Dicer1 knockout |
ISSN号 | 0260-437X |
DOI | 10.1002/jat.2973 |
文献子类 | Article |
英文摘要 | This study aims to evaluate the role of microRNAs (miRNAs) in chemical tumorigenesis by evaluating genomic gene expression in miRNA knockout mice. Previous studies showed that mice without mature miRNAs due to hepatocyte-specific Dicer1 knockout (KO) had a much higher liver tumor incidence than wild-type mice. In this study, Dicer1 KO or the wild-type mice were treated intraperitoneally with genotoxic carcinogen N-ethyl-N-nitrosourea (ENU) at a single dose (150 mg kg(-1) that resulted in liver tumorigenesis) or the vehicle at 3 weeks of age. The animals were killed 2 weeks after treatment and the liver samples were collected for the gene expression study. Principal components analysis and hierarchical cluster analysis showed that gene expression was globally altered by the Dicer1 KO and ENU exposure. There were 5621, 3286 and 2565 differentially expressed genes for Dicer1 disruption, ENU treatment in wild-type mice and ENU treatment in Dicer1 KO mice, respectively. Functional analysis of the differentially expressed genes suggests that the Dicer1 KO mouse liver lost their capability to suppress the carcinogenesis induced by ENU exposure in genomic level. In addition, the miRNA-mediated BRCA1 and P53 signaling pathways were identified as the main pathways responsible for the tumorigenesis. We conclude that the mouse livers in the absence of mature miRNAs could not appropriately respond to carcinogenic insults from ENU treatment, indicating that miRNAs play a critical role in chemical carcinogenesis. Copyright (c) 2014 John Wiley & Sons, Ltd. This study evaluates the role of microRNAs in chemical tumorigenesis by evaluating genomic gene expression in microRNA knockout mice treated with carcinogen N-ethyl-N-nitrosourea. The results demonstrate that the mouse liver in the absence of mature microRNAs could not appropriately respond to the carcinogenic insults to suppress the carcinogenesis induced by the carcinogen. Many tumor-suppressor functions, especially BRCA1 and P53 signaling pathways, were lost due to the absence of mature microRNAs. Thus, microRNAs play a critical role in chemical carcinogenesis. |
WOS关键词 | EMBRYONIC STEM-CELLS ; CHEMICAL CARCINOGENESIS ; RAT-LIVER ; PROFILES ; EXPOSURE ; DICER ; DIFFERENTIATION ; APOPTOSIS ; MIR-34A ; TUMORS |
WOS研究方向 | Toxicology |
语种 | 英语 |
WOS记录号 | WOS:000344146300016 |
出版者 | WILEY-BLACKWELL |
源URL | [http://119.78.100.183/handle/2S10ELR8/276824] ![]() |
专题 | 药物安全性评价中心 |
通讯作者 | Luan, Yang |
作者单位 | 1.Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab New Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Integrated Biotech Solut Co Ltd, Shanghai 201203, Peoples R China; 4.US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA |
推荐引用方式 GB/T 7714 | Luan, Yang,Qi, Xinming,Xu, Liang,et al. Absence of mature microRNAs inactivates the response of gene expression to carcinogenesis induced by N-ethyl-N-nitrosourea in mouse liver[J]. JOURNAL OF APPLIED TOXICOLOGY,2014,34(12):1409-1417. |
APA | Luan, Yang,Qi, Xinming,Xu, Liang,Ren, Jin,&Chen, Tao.(2014).Absence of mature microRNAs inactivates the response of gene expression to carcinogenesis induced by N-ethyl-N-nitrosourea in mouse liver.JOURNAL OF APPLIED TOXICOLOGY,34(12),1409-1417. |
MLA | Luan, Yang,et al."Absence of mature microRNAs inactivates the response of gene expression to carcinogenesis induced by N-ethyl-N-nitrosourea in mouse liver".JOURNAL OF APPLIED TOXICOLOGY 34.12(2014):1409-1417. |
入库方式: OAI收割
来源:上海药物研究所
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