PMID- 24101467
OWN - NLM
STAT- MEDLINE
DCOM- 20131230
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 110
IP  - 43
DP  - 2013 Oct 22
TI  - Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1 
      transcription.
PG  - 17480-5
LID - 10.1073/pnas.1312022110 [doi]
AB  - 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.
FAU - Xu, Bin
AU  - Xu B
AD  - 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.
FAU - Li, Shan-Hua
AU  - Li SH
FAU - Zheng, Rong
AU  - Zheng R
FAU - Gao, Shu-Bin
AU  - Gao SB
FAU - Ding, Li-Hong
AU  - Ding LH
FAU - Yin, Zhen-Yu
AU  - Yin ZY
FAU - Lin, Xiao
AU  - Lin X
FAU - Feng, Zi-Jie
AU  - Feng ZJ
FAU - Zhang, Sheng
AU  - Zhang S
FAU - Wang, Xiao-Min
AU  - Wang XM
FAU - Jin, Guang-Hui
AU  - Jin GH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131007
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, mouse)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics/metabolism
MH  - Animals
MH  - Carbon Tetrachloride/toxicity
MH  - Carcinogenesis/chemically induced/genetics/metabolism
MH  - Carcinoma, Hepatocellular/*genetics/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Chemical and Drug Induced Liver Injury/etiology/genetics/metabolism
MH  - Chromatin Immunoprecipitation
MH  - Diethylnitrosamine
MH  - Epigenesis, Genetic
MH  - Female
MH  - Hep G2 Cells
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Liver Neoplasms/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphoproteins/*genetics/metabolism
MH  - Proto-Oncogene Proteins/deficiency/*genetics
MH  - RNA Interference
MH  - Up-Regulation
MH  - Xenograft Model Antitumor Assays
MH  - YAP-Signaling Proteins
PMC - PMC3808599
OTO - NOTNLM
OT  - H3K4 methylation
OT  - interleukin 6
COIS- The authors declare no conflict of interest.
EDAT- 2013/10/09 06:00
MHDA- 2014/01/01 06:00
PMCR- 2014/04/22
CRDT- 2013/10/09 06:00
PHST- 2013/10/09 06:00 [entrez]
PHST- 2013/10/09 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2014/04/22 00:00 [pmc-release]
AID - 1312022110 [pii]
AID - 201312022 [pii]
AID - 10.1073/pnas.1312022110 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17480-5. doi: 
      10.1073/pnas.1312022110. Epub 2013 Oct 7.