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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; Xu, Liang3; Ren, Jin2; Chen, Tao4
刊名JOURNAL OF APPLIED TOXICOLOGY
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
DOI10.1002/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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