PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells.

Background: Prolyl hydroxylase domain proteins (PHD2) is an oxygen sensor that is able to induce hypoxia-inducible factor-α (HIF-α) degradation under normoxic condition. The present paper designed to reveal the function of PHD2 in hepatocellular carcinoma (HCC) cells proliferation, migration and invasion.Methods: qRT-PCR and Western blot were carried out to see the expression of PHD2 in HCC tissues and cell lines. PHD2 expression in Huh7 and HepG3B cells was overexpressed or suppressed by transfection and then the changes of cell proliferation, migration and invasion were detected by CCK-8 assay, transwell assay and Western blot.Results: PHD2 was highly expressed in HCC tissues and cell lines (Huh7, Hep3B, SK-HEP-1, HCCLM3 and MHCC97) as relative to para-cancerous non-tumour tissues and a normal hepatocyte line MIHA. PHD2 overexpression promoted Huh7 and Hep3B cells viability, migration and invasion. Meanwhile, CyclinD1, c-Myc, MMP-2, MMP-9 and Vimentin were up-regulated, while p53 was down-regulated by PHD2 overexpression. PHD2 silence led to a contrary impact. Further, PHD2 overexpression up-regulated Ras and Raf expression and induced phosphorylation of MEK, ERK, JAK1 and STAT3.Conclusion: PHD2 exhibited pro-tumour functions in HCC cells. PHD2 promoted HCC possibly through Ras/Raf/MEK/ERK and JAK1/STAT3 pathways.HighlightsPHD2 is highly expressed in HCC tissue and cell lines;PHD2 promotes the proliferation of Huh7 and HepG3B cells;PHD2 enhances Huh7 and HepG3B cells migration and invasion;PHD2 activates Ras/Raf/MEK/ERK and JAK1/STAT3 signalling.