The
GTPase-activating protein RLIP76 is overexpressed in and correlates with the pathological grade of many malignant
tumor cells. But the potential correlation between RLIP76 and clinical outcomes in patients with
meningioma remains unknown. In this study, we examined the expression of RLIP76 in
meningioma and correlated the RLIP76 expression to the patient outcome. RLIP76 expression in
tumor tissues was examined with immunohistochemistry, quantitative reverse-transcription polymerase chain reaction(RT-PCR) and Western-blot. Immunohistochemistry showed an increased RLIP76 immunostaining score in anaplastic and atypical
meningiomas versus classical
meningiomas. Statistical analyses revealed that RLIP76 immunostaining positively correlated with immunostaining for Ki-67, a
nuclear protein highly expressed in proliferating cells(r=0.29, p=0.034 by Spearman's correlation coefficient). Clinicopathological evaluation suggested that RLIP76 expression be associated with
tumor grade and recurrence(P<0.05). Univariate and Cox analysis indicated that RLIP76 was an independent prognostic factor for
tumor recurrence. Furthermore, the human malignant
meningioma cell lines IOMM-Lee and CH157-MN stably transfected with
short hairpin RNA (
siRNA) targeting RLIP76 were then examined by in vitro growth assays, and apoptosis assays. RLIP76 knockdown in IOMM-Lee and CH157-MN cells inhibited cell proliferation and induced apoptosis. Western blot analysis revealed that cells underexpressing RLIP76 exhibited decreased B-cell lymphoma-2(Bcl-2) expression but increased apoptosis effector
caspase-3 expression. These findings demonstrate that high RLIP76 expression is associated with a poor outcome of
meningioma and may provide a new gene therapy approach for patients with
malignant meningiomas.