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2015 ; 15
(ä): 990
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RIZ1: a potential tumor suppressor in glioma
#MMPMID26690953
Zhang C
; Zhu Q
; He H
; Jiang L
; Qiang Q
; Hu L
; Hu G
; Jiang Y
; Ding X
; Lu Y
BMC Cancer
2015[Dec]; 15
(ä): 990
PMID26690953
show ga
BACKGROUND: Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) displays
strong tumor suppressive activities, and its expression is often silenced in many
types of human tumors. However, the relationship between RIZ1 expression and
glioma prognosis remains unclear. METHODS: The dysregulation of RIZ1 was
evaluated using real-time polymerase chain reaction, western blot, and
immunohistochemical analysis of gliomas from 51 patients. Correlation analysis
was performed to examine relationships between RIZ1 immunoreactivity,
clinicopathological features, and patient prognosis. Also, human malignant glioma
U87 and U251 cell lines were stably transduced with ectogenic RIZ1 using a
lentiviral vector to investigate the effects of induced expression of RIZ1 on
cell proliferation, cell cycle, and apoptosis. RESULTS: Real-time polymerase
chain reaction and western blot analysis showed that RIZ1 was downregulated in
high-grade gliomas compared with low-grade gliomas and normal brain tissue.
Immunohistochemistry showed less RIZ1 labeling in high-grade gliomas than in
low-grade gliomas. There was a negative correlation between RIZ1 and Ki-67
immunoreactivity. Clinicopathological evaluation revealed that RIZ1 expression
was negatively correlated with tumor grade and patient age. Kaplan-Meier survival
analysis showed a positive correlation between RIZ1 immunoreactivity level and
progression-free and overall survival times. Multivariate analysis showed that
high RIZ1 expression was an independent prognostic factor for patients with
gliomas. Induced expression of RIZ1 in U87 and U251 cells reduced cell
proliferation and increased apoptosis, and cell cycle analysis revealed that a
majority of cells were arrested at G2-M. Moreover, transfection with a RIZ1
expression vector increased p53 and caspase-3 expression and decreased p-IKB? and
p-AKT protein levels, suggesting that RIZ1 may stimulate p53-mediated apoptosis
and inhibit p-IKB? and p-AKT signaling pathways. CONCLUSIONS: Our results suggest
that high RIZ1 labeling is indicative of lower grades of gliomas and is
associated with better progression-free and overall survival rates. Therefore,
RIZ1 may be a promising therapeutic target for patients with gliomas.