Abstract

As a member of the vasohibin (VASH2)family, VASH2 is localized intracellularly as a nuclear and cytoplasmic type.Cytoplasmic VASH2 is associated with carcinoma angiogenesis and malignanttransformation and promotes cancer growth. However, the function of nuclearVASH2 has yet to be investigated. The aim of the present study was to detectthe nuclear VASH2 expression profile in human organs and tissues by proteinmicroarray technique. To examine the function of nuclear VASH2, we analyzed therelationship between nuclear VASH2 and Ki-67, and stably constructed VASH2overexpression and knockdown in LO2 and HepG2 cell lines, based on a previousstudy in hepatic cells. The study was conducted using bromodeoxyuridine, immunofluorescentstaining, western blot analysis and flow cytometry. Nuclear VASH2 was highlyexpressed in actively dividing cells in normal and cancer tissues. There was asignificant positive correlation between nuclear VASH2 and Ki-67, indicatingthat nuclear VASH2 positively correlated with cell proliferation in normal andcancer tissues. The bromodeoxyuridine (BrdU) proliferation test showed thatnuclear VASH2 increased the S-phase population and promoted cell proliferation,while VASH2 knockdown reduced BrdU absorbance. Cell cycle analysis revealedthat nuclear VASH2 overexpression increased the S-phase population in LO2 andHepG2 cells, while nuclear VASH2 knockdown reduced the S-phase population andincreased the G0/G1 population. The findings of this study challenge theclassic view of VASH2, which was previously reported as an angiogenesis factor.Furthermore, to the best of our knowledge, these results are the first clinicaldata indicating that nuclear VASH2, but not cytoplasmic VASH2, promotes cell proliferationby driving the cell cycle from the G0/G1 to S phase.