title: Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis.
abstract: Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhongrun
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Clinical Laboratory, Longyan First Hospital, Fujian Medical University, Longyan, China.
authors.forename: Dingchang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Quanmin
authors.initials: Q
authors.lastname: Nie
authors.affiliation: Department of Pharmacology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Longyan First Hospital, Fujian Medical University, Longyan, China.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weiji
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingying
authors.identifier: 0000-0002-6935-5681
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D008822:Mice, Transgenic; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3
keywords: FoxO3a; MLL2; c-Myc; glioblastoma; prognosis