eRF3b, a biomarker for hepatocellular carcinoma, influences cell cycle and phosphoralation status of 4E-BP1

• Published in: PloS one 2014-01, Vol.9 (1), p.e86371
• Main Authors: Li, Man, Wang, Jian, Yang, Lei, Gao, Ping, Tian, Qing-Bao, Liu, Dian-Wu
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - blood; Adaptor Proteins, Signal Transducing - metabolism; Adolescent; Adult; Aged; Amino Acid Sequence; Analysis; Area Under Curve; Beads; Biology; Biomarkers; Biomarkers, Tumor - blood; Carcinoma, Hepatocellular - blood; Cation exchanging; Cell Cycle; Child; Complications; Cytoskeleton; Disease; Epidemiology; Gene expression; GTP; Guanosine triphosphate; Health aspects; Hep G2 Cells; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatocellular carcinoma; Humans; Identification; Ionization; Liver; Liver - metabolism; Liver - pathology; Liver cancer; Liver Neoplasms - blood; Mass spectrometry; Mass spectroscopy; Medicine; Middle Aged; Molecular Sequence Data; mRNA; Patients; Peptide Termination Factors - blood; Peptide Termination Factors - metabolism; Phosphoproteins - blood; Phosphoproteins - metabolism; Phosphorylation; Polypeptides; Protein Processing, Post-Translational; Proteins; RNA; ROC Curve; rRNA 18S; Scientific imaging; Signal Transduction; Standard deviation; Substrates; Tissues; TOR protein; TOR Serine-Threonine Kinases - metabolism; Viruses; Yeast; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086371

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. 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. 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.