RGD Reference Report - Hepatitis B virus X protein mediated suppression of miRNA-122 expression enhances hepatoblastoma cell proliferation through cyclin G1-p53 axis. - Rat Genome Database

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Hepatitis B virus X protein mediated suppression of miRNA-122 expression enhances hepatoblastoma cell proliferation through cyclin G1-p53 axis.

Authors: Bandopadhyay, Manikankana  Sarkar, Neelakshi  Datta, Sibnarayan  Das, Dipanwita  Pal, Ananya  Panigrahi, Rajesh  Banerjee, Arup  Panda, Chinmay K  Das, Chandrima  Chakrabarti, Shekhar  Chakravarty, Runu 
Citation: Bandopadhyay M, etal., Infect Agent Cancer. 2016 Aug 15;11:40. doi: 10.1186/s13027-016-0085-6. eCollection 2016.
RGD ID: 151361113
Pubmed: PMID:27528885   (View Abstract at PubMed)
PMCID: PMC4983788   (View Article at PubMed Central)
DOI: DOI:10.1186/s13027-016-0085-6   (Journal Full-text)


BACKGROUND: Hepatitis B virus (HBV) X protein (HBx) reported to be associated with pathogenesis of hepatocellular carcinoma (HCC) and miR-122 expression is down regulated in HCC. Previous studies reported miR-122 targets cyclin G1 (CCNG1) expression and this in turn abolishes p53-mediated inhibition of HBV replication. Here we investigated the involvement of HBx protein in the modulation of miR-122 expression in hepatoblastoma cells.
METHODS: Expression of miR-122 was measured in HepG2 cells transfected with HBx plasmid (HBx-HepG2), full length HBV genome (HBV-HepG2) and in constitutively HBV synthesizing HepG2.2.15 cells. CCNG1 mRNA (a direct target of miR-122) and protein expressions were also measured in both HBx-HepG2, HBV-HepG2 cells and in HepG2.2.15 cells. miR-122 expressions were analyzed in HBx-HepG2, HBV-HepG2 and in HepG2.2.15 cells after treatment with HBx mRNA specific siRNA. Expressions of p53 mRNA and protein which is negatively regulated by CCNG1 were analyzed in HBx transfected HepG2 cells; X silenced HBx-HepG2 cells and X silenced HepG2.2.15 cells. HBx induced cell proliferation in HepG2 cells was measured by cell proliferation assay. Flow cytometry was used to evaluate changes in cell cycle distribution. Expression of cell cycle markers were measured by real time PCR.
RESULTS: Expression of miR-122 was down regulated in HBx-HepG2, HBV-HepG2 and also in HepG2.2.15 cell line compared to control HepG2 cells. CCNG1 expression was found to be up regulated in HBx-HepG2, HBV-HepG2 cells and in HepG2.2.15 cells. Following siRNA mediated silencing of HBx expression; increased miR-122 levels were documented in HBx-HepG2, HBV-HepG2 and in HepG2.2.15 cells. HBx silencing in HBx-HepG2 and HepG2.2.15 cells also resulted in increased p53 expression. FACS analysis and assessment of expressions of cell cycle markers revealed HBx induced a release from G1/S arrest in HepG2 cells. Further, cell proliferation assay showed HBx promoted proliferation of HepG2 cell.
CONCLUSION: Our study revealed that HBx induced down regulation of miR-122 expression that consequently increased CCNG1 expression. This subsequently caused cell proliferation and release from G1/S arrest in malignant hepatocytes. The study provides the potential to utilize the HBx-miR-122 interaction as a therapeutic target to limit the development of HBV related HCC.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MIR122Humanhepatocellular carcinoma  IEP mRNA:decreased expression:blood (human)RGD 
Mir122Mousehepatocellular carcinoma  ISOMIR122 (Homo sapiens)mRNA:decreased expression:blood (human)RGD 
Mir122Rathepatocellular carcinoma  ISOMIR122 (Homo sapiens)mRNA:decreased expression:blood (human)RGD 
MIR122Humanliver cirrhosis  IEP mRNA:decreased expression:blood (human)RGD 
Mir122Mouseliver cirrhosis  ISOMIR122 (Homo sapiens)mRNA:decreased expression:blood (human)RGD 
Mir122Ratliver cirrhosis  ISOMIR122 (Homo sapiens)mRNA:decreased expression:blood (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir122  (microRNA 122)

Genes (Mus musculus)
Mir122  (microRNA 122)

Genes (Homo sapiens)
MIR122  (microRNA 122)


Additional Information