OBJECTIVETo investigate the expression of esophageal cancer related gene 4 (ECRG4) in human hepatocellular carcinoma and the role of ECRG4 in proliferation, apoptosis and migration of hepatoma cells.

METHODSECRG4 expression was investigated in normal or tumor liver cell lines including QSG7701 and HepG2 cells, and in 24 pairs of fresh samples of hepatocellular carcinoma by quantitative real-time PCR or Western blot. ECRG4-pcDNA3.1 expressing plasmid was transfected into HepG2 cells, of which cellular proliferation, apoptosis and migration were documented.

RESULTSECRG4 mRNA expression was reduced or absent in most primary hepatocellular carcinoma samples (95.8%, 23 out of 24 hepatocellular carcinoma samples) compared to their paired normal liver samples (P < 0.01). ECRG4 mRNA was significantly lower in HepG2 cells than QSG7701 cells (P < 0.05) along with decreased ECRG4 protein expression. HepG2 cells overexpressing ECRG4 showed decreased proliferation, increased apoptosis and reduced migration as compared with control cells (P < 0.05).

CONCLUSIONSECRG4 expression is frequently down-regulated in hepatocellular carcinoma. Overexpression of ECRG4 inhibits the proliferation and migration but promotes apoptosis of HepG2 cells, suggesting that ECRG4 is a candidate tumor suppressor gene in hepatocellular carcinoma and therefore may serve as a novel target for precision therapy.

Apoptosis ; Blotting, Western ; Carcinoma, Hepatocellular ; metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; Neoplasm Proteins ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Transfection