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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Xu, Bin Gao, Shu-bin Li, Shan-hua Yin, Zhen-yu Wang, Xiao-min Zheng, Rong Feng, Zi-jie Ding, Li-hong Zhang, Sheng Jin, Guang-hui Lin, Xiao |
| Description | Author Affiliation: Xu B ( Department of Basic Medical Sciences of Medical College, State Key Laboratory of Cellular Stress Biology, and Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University, Xiamen 361102, People's Republic of China.); |
| Abstract | Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene in humans, and it interacts with a variety of transcriptional proteins to control active or repressive cellular processes. Here, we show that heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced liver carcinogenesis and represses the activation of the inflammation pathway. Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy frequently coincides with H3K4me3 at the promoter of many liver cancer-related genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression in human hepatocellular carcinoma specimens was associated with poor prognosis. Our findings reveal that menin plays an important epigenetic role in promoting liver tumorigenesis, and support the notion that H3K4me3, which is regulated by the menin-mixed-lineage leukemia complex, is a potential therapeutic target in hepatocellular carcinoma. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adaptor Proteins, Signal Transducing Genetics Carcinoma, Hepatocellular Liver Neoplasms Phosphoproteins Proto-Oncogene Proteins Metabolism Animals Carbon Tetrachloride Toxicity Carcinogenesis Chemically Induced Cell Line, Tumor Drug-Induced Liver Injury Etiology Chromatin Immunoprecipitation Diethylnitrosamine Epigenesis, Genetic Hep G2 Cells Kaplan-Meier Estimate Mice Mice, Inbred C57BL Mice, Knockout Mice, Nude Oligonucleotide Array Sequence Analysis Deficiency RNA Interference Up-Regulation Xenograft Model Antitumor Assays Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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