Screening of hepatoma-derived growth factor with highly expression in HCC bone metastasis and its cellular biological effects

To investigate the expression of hepatoma-derived growth factor (HDGF) in hepatocellular carcinoma (HCC) and its effects on DNA damage, proliferation, migration, epithelial mesenchymal transition (EMT), and expression of osteoprotegerin (OPG) in HCC cells.

GEO database was analyzed to obtain the expression features of differential expressed mRNAs in liver tumors between HCC patients with bone metastasis and those without, and then HDGF was found as the most significantly differentially expressed gene. The mRNA expression of HDGF was verified in the HCC cells with varying metastatic capabilities by qRT-PCR. DNA damage levels in different groups of liver cancer cells were analyzed through γ-H2AX immunofluorescence assay. The effects of HDGF on cell proliferation and migration were detected with CCK-8 assay, colony formation assay, and Transwell migration assay. Western blotting was employed to measure the expression of EMT-related proteins Vimentin and E-cadherin in HCC cells with various capacities of bone metastasis. Then qRT-PCR and Western blotting were performed to determine the differential expression of OPG in various groups of liver cancer cells.

HDGF was highly expressed in HCC tissues with bone metastasis and in high-metastatic HCC cell lines. High expression of HDGF inhibited DNA damage repair. HDGF promoted the proliferation and migration of HCC cell lines. HDGF up-regulated the protein expression level of Vimentin while down-regulated that of E-cadherin (both P < 0.05), and overexpression of HDGF down-regulated the expression of OPG.

HDGF is highly expressed in bone metastatic hepatocellular tumors and may promote bone metastasis by facilitating EMT, migration, and proliferation.