Lei Wang1, Jingchao Wang2, Tong Jin3, Yi Zhou4, Qianxue Chen5. 1. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China. 2. Medical Research Institute, Wuhan University, Wuhan, 430071, China. 3. Renmin Hospital of Wuhan University, Wuhan, 430060, China. 4. Department of Neurosurgery, Renmin Hospital of Hubei University of Medicine, Hubei, 442000, China. 5. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: chenqx666@whu.edu.cn.
Abstract
BACKGROUND: To investigate the effects and underlying molecular mechanisms of FoxG1 expression on glioblastoma multiforme (GBM) models. METHODS: Expression levels of FoxG1 and other cancer-related biomarkers were evaluated by qRT-PCR, immunoblotting and immunohistochemistry. Crystal violet staining and MTT assay and were applied in this study to verify cell proliferation ability and viability of GBM cell models with/without drug treatment. RESULTS: Immunohistochemical and qRT-PCR assays showed that endogenous FoxG1 expression levels were positively correlated to the GBM disease progression. Overexpression of FoxG1 protein resulted in increased cell viability, G2/M cell cycle arrest, as well as the downregulation of p21 and cyclin B1. In addition, western blot assays reported that enforced expression of FoxG1 suppressed GAPF and facilitated the expression of Sox2 and Sox5. Meanwhile the downstream targets of FoxG1, such as FoxO1 and pSmad1/5/8 were activated. Overexpression of FoxG1 under TMZ treatment restored the cell viability as well as the expression levels of Sox2 and Sox5, yet downregulated expression levels of p21 and cyclin B1. The downstream FoxG1-induced FoxO/Smad signaling was re-inhibited under TMZ treatments. CONCLUSIONS: Our findings suggest that FoxG1 functions as an onco-factor by promoting proliferation, as well as inhibiting differential responses in glioblastoma by downregulating FoxO/Smad signaling.
BACKGROUND: To investigate the effects and underlying molecular mechanisms of FoxG1 expression on glioblastoma multiforme (GBM) models. METHODS: Expression levels of FoxG1 and other cancer-related biomarkers were evaluated by qRT-PCR, immunoblotting and immunohistochemistry. Crystal violet staining and MTT assay and were applied in this study to verify cell proliferation ability and viability of GBM cell models with/without drug treatment. RESULTS: Immunohistochemical and qRT-PCR assays showed that endogenous FoxG1 expression levels were positively correlated to the GBM disease progression. Overexpression of FoxG1 protein resulted in increased cell viability, G2/M cell cycle arrest, as well as the downregulation of p21 and cyclin B1. In addition, western blot assays reported that enforced expression of FoxG1 suppressed GAPF and facilitated the expression of Sox2 and Sox5. Meanwhile the downstream targets of FoxG1, such as FoxO1 and pSmad1/5/8 were activated. Overexpression of FoxG1 under TMZ treatment restored the cell viability as well as the expression levels of Sox2 and Sox5, yet downregulated expression levels of p21 and cyclin B1. The downstream FoxG1-induced FoxO/Smad signaling was re-inhibited under TMZ treatments. CONCLUSIONS: Our findings suggest that FoxG1 functions as an onco-factor by promoting proliferation, as well as inhibiting differential responses in glioblastoma by downregulating FoxO/Smad signaling.
Authors: Valentina Bravatà; Walter Tinganelli; Francesco P Cammarata; Luigi Minafra; Marco Calvaruso; Olga Sokol; Giada Petringa; Giuseppe A P Cirrone; Emanuele Scifoni; Giusi I Forte; Giorgio Russo Journal: J Pers Med Date: 2021-04-16
Authors: Benjamen T O'Donnell; Tia A Monjure; Sara Al-Ghadban; Clara J Ives; Michael P L'Ecuyer; Claire Rhee; Monica Romero-Lopez; Zhong Li; Stuart B Goodman; Hang Lin; Rocky S Tuan; Bruce A Bunnell Journal: Cells Date: 2022-08-01 Impact factor: 7.666