title: Overexpression of RLIP76 Required for Proliferation in Meningioma Is Associated with Recurrence.
abstract: 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.
authors.affiliation: Department of Neurosurgery, PLA No.322 hospital, 2 Yunzhong Road, Shanxi 03700,China.
authors.forename: Song-Yuan
authors.initials: SY
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, the 174th hospital of PLA (Chenggong Hospital, Xiamen University), Xiamen 361003, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Guo-Han
authors.initials: GH
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, PLA No.322 hospital, 2 Yunzhong Road, Shanxi 03700,China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Hou
authors.affiliation: Department of Neurosurgery, PLA No.322 hospital, 2 Yunzhong Road, Shanxi 03700,China; Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D008579:Meningioma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C095637:RALBP1 protein, human; D034741:RNA, Small Interfering; D053148:Caspase 3