RGD Reference Report - HBx protein-mediated ATOH1 downregulation suppresses ARID2 expression and promotes hepatocellular carcinoma. - Rat Genome Database

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HBx protein-mediated ATOH1 downregulation suppresses ARID2 expression and promotes hepatocellular carcinoma.

Authors: Gao, Qingzhu  Wang, Kai  Chen, Ke  Liang, Li  Zheng, Yaqiu  Zhang, Yunzhi  Xiang, Jin  Tang, Ni 
Citation: Gao Q, etal., Cancer Sci. 2017 Jul;108(7):1328-1337. doi: 10.1111/cas.13277. Epub 2017 Jun 14.
RGD ID: 150340712
Pubmed: PMID:28498550   (View Abstract at PubMed)
PMCID: PMC5497798   (View Article at PubMed Central)
DOI: DOI:10.1111/cas.13277   (Journal Full-text)

Hepatitis B virus X protein plays a crucial role in the pathogenesis of hepatocellular carcinoma. We previously showed that the tumor suppressor ARID2 inhibits hepatoma cell cycle progression and tumor growth. Here, we evaluated whether hepatitis B virus X protein was involved in the modulation of ARID2 expression and hepatocarcinogenesis associated with hepatitis B virus infection. ARID2 expression was downregulated in HBV-replicative hepatoma cells, HBV transgenic mice, and HBV-related clinical HCC tissues. The expression levels of HBx were negatively associated with those of ARID2 in hepatocellular carcinoma tissues. Furthermore, HBx suppressed ARID2 at transcriptional level. Mechanistically, the promoter region of ARID2 gene inhibited by HBx was located at nt-1040/nt-601 and contained potential ATOH1 binding elements. In addition, ectopic expression of ATOH1 or mutation of ATOH1 binding sites within ARID2 promoter partially abolished HBx-triggered ARID2 transcriptional repression. Functionally, ARID2 abrogated HBx-enhanced migration and proliferation of hepatoma cells, whereas depletion of ATOH1 enhanced tumorigenecity of HCC cells. Therefore, our findings suggested that deregulation of ARID2 by HBx through ATOH1 may be involved in HBV-related hepatocellular carcinoma development.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARID2Humanhepatocellular carcinoma  IEP associated with hepatitis B and protein:decreased expression:liverRGD 
Arid2Rathepatocellular carcinoma  ISOARID2 (Homo sapiens)associated with hepatitis B and protein:decreased expression:liverRGD 
Arid2Mousehepatocellular carcinoma  ISOARID2 (Homo sapiens)associated with hepatitis B and protein:decreased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Arid2  (AT-rich interaction domain 2)

Genes (Mus musculus)
Arid2  (AT-rich interaction domain 2)

Genes (Homo sapiens)
ARID2  (AT-rich interaction domain 2)


Additional Information