RGD Reference Report - HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. - Rat Genome Database

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HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis.

Authors: Vazquez-Chantada, M  Fernandez-Ramos, D  Embade, N  Martinez-Lopez, N  Varela-Rey, M  Woodhoo, A  Luka, Z  Wagner, C  Anglim, PP  Finnell, RH  Caballeria, J  Laird-Offringa, IA  Gorospe, M  Lu, SC  Mato, JM  Martinez-Chantar, ML 
Citation: Vazquez-Chantada M, etal., Gastroenterology. 2010 May;138(5):1943-53. doi: 10.1053/j.gastro.2010.01.032. Epub 2010 Jan 25.
RGD ID: 10042969
Pubmed: PMID:20102719   (View Abstract at PubMed)
PMCID: PMC2860011   (View Article at PubMed Central)
DOI: DOI:10.1053/j.gastro.2010.01.032   (Journal Full-text)

BACKGROUND & AIMS: Hepatic de-differentiation, liver development, and malignant transformation are processes in which the levels of hepatic S-adenosylmethionine are tightly regulated by 2 genes: methionine adenosyltransferase 1A (MAT1A) and methionine adenosyltransferase 2A (MAT2A). MAT1A is expressed in the adult liver, whereas MAT2A expression primarily is extrahepatic and is associated strongly with liver proliferation. The mechanisms that regulate these expression patterns are not completely understood. METHODS: In silico analysis of the 3' untranslated region of MAT1A and MAT2A revealed putative binding sites for the RNA-binding proteins AU-rich RNA binding factor 1 (AUF1) and HuR, respectively. We investigated the posttranscriptional regulation of MAT1A and MAT2A by AUF1, HuR, and methyl-HuR in the aforementioned biological processes. RESULTS: During hepatic de-differentiation, the switch between MAT1A and MAT2A coincided with an increase in HuR and AUF1 expression. S-adenosylmethionine treatment altered this homeostasis by shifting the balance of AUF1 and methyl-HuR/HuR, which was identified as an inhibitor of MAT2A messenger RNA (mRNA) stability. We also observed a similar temporal distribution and a functional link between HuR, methyl-HuR, AUF1, and MAT1A and MAT2A during fetal liver development. Immunofluorescent analysis revealed increased levels of HuR and AUF1, and a decrease in methyl-HuR levels in human livers with hepatocellular carcinoma (HCC). CONCLUSIONS: Our data strongly support a role for AUF1 and HuR/methyl-HuR in liver de-differentiation, development, and human HCC progression through the posttranslational regulation of MAT1A and MAT2A mRNAs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma  IEP 10042969protein:increased expression:liver (human)RGD 
hepatocellular carcinoma  ISOHNRNPD (Homo sapiens)10042969; 10042969protein:increased expression:liver (human)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocyte dedifferentiation  IEP 10042969 RGD 
liver development  IEP 10042969 RGD 
positive regulation of gene expression  IMP 10042969Mat1aRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hnrnpd  (heterogeneous nuclear ribonucleoprotein D)

Genes (Mus musculus)
Hnrnpd  (heterogeneous nuclear ribonucleoprotein D)

Genes (Homo sapiens)
HNRNPD  (heterogeneous nuclear ribonucleoprotein D)

Additional Information