eRF3b, a biomarker for hepatocellular carcinoma, influences cell cycle and phosphoralation status of 4E-BP1.
BACKGROUND
Hepatitis B virus (HBV) infection and its sequelae are now recognized as serious problems globally. Our aime is to screen hepatocellular carcinoma (HCC) from chronic hepatitis B (CHB) and identify the characteristics of proteins involved.


RESULTS
We affinity-purified sample serum with weak cation-exchange (WCX) magnetic beads and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis to search for potential markers. The 4210 Da protein, which differed substantially between HCC and CHB isolates, was later identified to be eukaryotic peptide chain release factor GTP-binding subunit eRF3b. Further research showed that eRF3b/GSPT2 was positively expressed in liver tissues. GSPT2 mRNA was, however differentially expressed in blood. Compared with normal controls, the relative expression of GSPT2/18s rRNA was higher in CHB patients than in patients with either LC or HCC (P = 0.035 for CHB vs. LC; P = 0.020 for CHB vs. HCC). The data of further research showed that eRF3b/GSPT2 promoted the entrance of the HepG2 cells into the S-phase and that one of the substrates of the mTOR kinase, 4E-BP1, was hyperphosphorylated in eRF3b-overexpressing HepG2 cells.


CONCLUSIONS
Overall, the differentially expressed protein eRF3b, which was discovered as a biomarker for HCC, could change the cell cycle and influence the phosphorylation status of 4E-BP1 on Ser65 in HepG2.
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Man
M
Li
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China ; Department of Epidemiology, Hebei North University, Zhangjiakou, Hebei Province, China.
Jian
J
Wang
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Lei
L
Yang
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Ping
P
Gao
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Qing-Bao
QB
Tian
Department of Epidemiology and Statistic, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Dian-Wu
DW
Liu
D048868:Adaptor Proteins, Signal Transducing / Q000097:blood* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002648:Child; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors / Q000097:blood* / Q000378:metabolism*; D010750:Phosphoproteins / Q000097:blood* / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012372:ROC Curve; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010454:Peptide Termination Factors; D010750:Phosphoproteins; C087971:peptide-chain-release factor 3; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases