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Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis.
- Source :
-
International journal of cancer [Int J Cancer] 2017 Jun 15; Vol. 140 (12), pp. 2792-2804. Date of Electronic Publication: 2017 Apr 03. - Publication Year :
- 2017
-
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.<br /> (© 2017 UICC.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Animals
Blotting, Western
Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Line, Tumor
Disease Progression
Female
Forkhead Box Protein O3 metabolism
Glioblastoma metabolism
Glioblastoma pathology
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Mice, Nude
Mice, Transgenic
Middle Aged
Neoplasm Invasiveness
Prognosis
RNA Interference
Transplantation, Heterologous
Young Adult
Brain Neoplasms genetics
Forkhead Box Protein O3 genetics
Gene Expression Regulation, Neoplastic
Glioblastoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 140
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 28295288
- Full Text :
- https://doi.org/10.1002/ijc.30690