High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma

Pathol Res Pract. 2016 Mar;212(3):171-8. doi: 10.1016/j.prp.2015.11.015. Epub 2015 Nov 28.

Abstract

VRK1 is a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which is known to play multiple roles in cellular proliferation, cell cycle regulation and carcinogenesis. However, the expression and physiological significance of VRK1 in hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to investigate the potential role of VRK1 in the development and progression of HCC. Western blot and immunohistochemical analysis revealed that VRK1 was highly expressed in HCC tissues and cell lines, compared with adjacent nontumorous tissues and LO2 normal hepatocytes. Meanwhile, clinicopathological analysis showed that VRK1 was significantly associated with AJCC stage, Ki-67 and a poor prognosis in HCC specimens. Univariate and multivariate analysis showed that VRK1 could serve as an independent prognostic indicator of HCC patients' survival. Furthermore, we found that VRK1 was lowly expressed in serum-starved Huh7 cells, and was progressively increased after serum-refeeding. Finally, flow cytometry, CCK-8 and colony formation assay indicated that the depletion of VRK1 could retard cell cycle progression and reduce cells proliferation in HCC cells. On the basis of these findings, we conclude that VRK1 may be a candidate prognostic biomarker as well as a potential therapeutical target of HCC.

Keywords: Cell proliferation; Hepatocellular carcinoma; Prognosis; VRK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / biosynthesis
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation*
  • Cell Survival
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • VRK1 protein, human