title: Nuclear vasohibin-2 promotes cell proliferation by inducing G0/G1 to S phase progression.
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 malignant transformation and promotes cancer growth. However, the function of nuclear VASH2 has yet to be investigated. The aim of the present study was to detect the nuclear VASH2 expression profile in human organs and tissues by protein microarray technique. To examine the function of nuclear VASH2, we analyzed the relationship between nuclear VASH2 and Ki-67, and stably constructed VASH2 overexpression and knockdown in LO2 and HepG2 cell lines, based on a previous study in hepatic cells. The study was conducted using bromodeoxyuridine, immunofluorescent staining, western blot analysis and flow cytometry. Nuclear VASH2 was highly expressed in actively dividing cells in normal and cancer tissues. There was a significant positive correlation between nuclear VASH2 and Ki-67, indicating that nuclear VASH2 positively correlated with cell proliferation in normal and cancer tissues. The bromodeoxyuridine (BrdU) proliferation test showed that nuclear VASH2 increased the S-phase population and promoted cell proliferation, while VASH2 knockdown reduced BrdU absorbance. Cell cycle analysis revealed that nuclear VASH2 overexpression increased the S-phase population in LO2 and HepG2 cells, while nuclear VASH2 knockdown reduced the S-phase population and increased the G0/G1 population. The findings of this study challenge the classic view of VASH2, which was previously reported as an angiogenesis factor. Furthermore, to the best of our knowledge, these results are the first clinical data indicating that nuclear VASH2, but not cytoplasmic VASH2, promotes cell proliferation by driving the cell cycle from the G0/G1 to S phase.
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Ge
authors.affiliation: The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Jishu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Song
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Kuirong
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Gao
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D040081:Protein Array Analysis; D016196:S Phase / Q000235:genetics
chemical_list: D042501:Angiogenic Proteins; D019394:Ki-67 Antigen; C574858:VASH2 protein, human