RGD Reference Report - MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms. - Rat Genome Database

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MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms.

Authors: Wang, Yu  Toh, Han Chong  Chow, Pierce  Chung, Alexander Y F  Meyers, David J  Cole, Philip A  Ooi, London L P J  Lee, Caroline G L 
Citation: Wang Y, etal., FASEB J. 2012 Jul;26(7):3032-41. doi: 10.1096/fj.11-201855. Epub 2012 Mar 29.
RGD ID: 18182922
Pubmed: (View Article at PubMed) PMID:22459148
DOI: Full-text: DOI:10.1096/fj.11-201855

MicroRNA-224 (miR-224) is one of the most commonly up-regulated microRNAs in hepatocellular carcinoma (HCC), which affects crucial cellular processes such as apoptosis and cell proliferation. In this study, we aim to elucidate the molecular mechanism that leads to the overexpression of miR-224 in HCC. We examined the transcript expression of miR-224 and neighboring miR-452 and genes on chromosome Xq28 in tumor and paired adjacent nontumorous tissues from 100 patients with HCC and found that miR-224 is coordinately up-regulated with its neighboring microRNA (miRNA) and genes. This coordinated up-regulation of miRNAs and genes at the Xq28 locus can be mimicked in nontransformed immortalized human liver cells by the introduction of histone deacetylase (HDAC) inhibitors, which resulted in a corresponding increase in histone H3 acetylation in this region. This miR-224-residing locus in Xq28 is reciprocally regulated by HDAC1, HDAC3, and histone acetylase protein, E1A binding protein p300 (EP300). Notably, in HCC tumors that significantly overexpress microRNA-224, EP300 is also overexpressed and displays increased binding to the Xq28 locus. In transformed HCC cells, high miR-224 expression can be attenuated through the inhibition of EP300, using either siRNA or the specific drug C646. In summary, overexpression of EP300 may account, in part, for the up-regulation of miR-224 expression in patients with HCC.


Disease Annotations    

Gene-Chemical Interaction Annotations    
C646  (EXP,ISO)
trichostatin A  (EXP,ISO)
vorinostat  (EXP)

Objects Annotated

Genes (Rattus norvegicus)
Mir224  (microRNA 224)

Genes (Mus musculus)
Mir224  (microRNA 224)

Genes (Homo sapiens)
MIR224  (microRNA 224)

Additional Information