Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

Cui, Lishan; Xu, Shaohua; Song, Zhengmao; Zhao, Gang; Liu, Xiaoqian; Song, Yuwen

doi:10.1093/abbs/gmv026

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…MVD is an important index for the detection of tumor angiogenesis which is assessed by the immunochemistry staining of CD31. Consistent with Cui et al ( 23 ), our study revealed that the expression of CD31 was highly expressed in glioma tissues, which indicated that angiogenesis in glioma was higher than in normal brain tissues. LRIG2 expression in glioma tissues was positivity correlated with the MVD.…”

Section: Discussionsupporting

confidence: 92%

Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway

et al. 2017

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Active angiogenesis is the basic pathological feature of glioma. Tumor angiogenesis is involved in vascular endothelial cell migration to the tumor tissue and in the formation of tube-like structures. The present study aimed to investigate the role of leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) in glioma angiogenesis. Glioma (n=50) and normal brain (n=20) tissue samples were collected from patients to detect the expression of LRIG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGF-A), and cluster of differentiation 31 (CD31) using immunohistochemistry. In addition, the association between the expression of LRIG2 in glioma tissue and the microvessel density (MVD) was analyzed. In vitro, the expression of LRIG2 in human glioma U87 and U251 cell lines was knocked down. Subsequently, cell migration and tube formation assays of human umbilical vein endothelial cells (HUVECs) were performed using a coculture system. The protein expression levels of LRIG2, EGFR, phosphorylated-EGFR and VEGF-A were determined using western blotting. The results demonstrated that the expression levels of LRIG2, EGFR, VEGF-A and CD31 were highly upregulated in glioma tissue samples. Furthermore, LRIG2 expression in glioma tissue samples was significantly correlated with the MVD. In vitro, the downregulation of LRIG2 inhibited HUVEC migration and tube formation induced by coculture with glioma cells. The downregulation of LRIG2 resulted in decreased expression of EGFR and VEGF-A. The effects of the LRIG2 knockdown were reversed following EGF treatment. These findings suggest that LRIG2 is a potential target for the inhibition of glioma angiogenesis, which is possibly mediated via the EGFR/VEGF-A signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway

et al. 2017

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“…It was demonstrated that the expression level of VEGF mRNA in patients with grade III and IV gliomas was significantly higher than that in patients with grade I and II gliomas, and the expression level of VEGF mRNA in patients with grade I and II gliomas was significantly higher than that in normal brain tissues (25)(26)(27). In addition, the cell viability, migration and invasion, and angiogenesis of gliomas may be inhibited by inhibition of the pituitary tumor transforming gene that was positively associated with the glioma grade and tumor microvessel density (28), and was considered as an important target of glioma antiangiogenic therapy. It was also demonstrated that certain angiogenic chemokines secreted by tumor cells may directly effect vascular ECs, which induces angiogenesis (29).…”

Section: Discussionmentioning

confidence: 90%

miR‑24 regulates angiogenesis in gliomas

Dai

Huang

et al. 2018

Mol Med Report

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Gliomas are one of the most common and most aggressive types of central nervous system tumor. Angiogenesis is an important basis for the growth of solid tumors, including gliomas, which is regulated by microRNAs (miRNAs). However, the mechanism remains unclear. Recently, it was demonstrated that miR‑24 was upregulated in gliomas, so the aim of the present study is to establish whether the dysregulation of miR‑24 in glioma cells promotes microvascular proliferation of endothelial cells (ECs), and to investigate the potential mechanism. miR‑24 was overexpressed or downregulated in U251 glioma cell line cells using miR‑24 mimics or inhibitors, respectively. Subsequently, the effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on cell viability, migration and angiogenesis of human umbilical vein ECs (HUVECs) were examined. The expression levels of vascular endothelial growth factor (VEGF) mRNA, basic fibroblast growth factor (bFGF) mRNA, epidermal growth factor (EGF) mRNA, transforming growth factor (TGF)‑β mRNA, matrix metalloproteinase (MMP)‑2 mRNA and MMP‑9 mRNA, and the mRNA and protein levels of VEGF and TGF‑β in miR‑24 mimic‑ or inhibitor‑transfected U251 cells were obtained by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on expression levels of VEGF mRNA, TGF‑β mRNA, MMP‑2 mRNA and MMP‑9 mRNA, and mRNA and protein expression levels of VEGF and TGF‑β, and intracellular AKT and β‑catenin signaling in HUVECs were also examined. The results indicated that the conditional medium from miR‑24 mimic‑transfected U251 cells exhibited significantly increased cell viability, cell migration and tube formation of HUVECs. By contrast, the conditional medium from miR‑24 inhibitor‑transfected U251 cells exhibited significantly decreased cell viability, cell migration and tube formation of HUVECs. Enforced expression of miR‑24 in U251 cells may promote the cell viability and angiogenesis of HUVECs. The mRNA expression levels of VEGF, bFGF, EGF, TGF‑β, MMP‑2 and MMP‑9 in U251 cells were significantly increased by miR‑24 mimics. Western blot detection confirmed the increased levels of VEGF and TGF‑β protein expression in U251 by miR‑24 mimics, and the decrease of VEGF and TGF‑β protein expression levels in U251 by miR‑24 inhibitors. The conditional medium from miR‑24 mimic‑transfected U251 cells increased the expression levels of the angiogenesis‑associated factors, including VEGF, TGF‑β, MMP‑2, and MMP‑9. By contrast, reduced expression of miR‑24 in U251 cells may downregulate the expression of those angiogenesis‑associated factors. Thus, miR‑24 in U251 cells may be important in the angiogenesis of HUVECs via VEGF and TGF‑β, and the intracellular signaling of AKT and β‑catenin may be involved in this process.

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“…This gene plays important roles in cell proliferation and transformation, and the protein expressed from PTTG (securin) has been shown to be responsible for chromatid separation in mitosis 69. Studies have shown that PTTG is involved in the migration and invasion of glioma, suggesting the role of PTTG as a diagnostic and therapeutic target for glioma 70-73. Increased expression of PTTG in the tumor tissues has been found in various tumors, including glioma 71, 74, and has been shown to be related to the poor prognosis of glioma patients 71.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of serum extracellular vesicles as noninvasive diagnostic markers of glioma

Wang¹,

Jiang

et al. 2019

Theranostics

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Rationale : Glioma is the most common malignant primary brain tumor in the central nervous system (CNS). The lack of reliable noninvasive diagnostic and prognostic methods is one of the main reasons for the high mortality of glioma. Serum has become a useful biomarker for the diagnosis and prognosis prediction of glioma because extracellular vesicles (EVs) carry molecular components from their parental cells. Methods : To detect EVs and perform molecular analysis of serum EVs, we established and optimized a microbead-assisted method based on flow cytometry and estimated the efficacy of EGFR protein expression and NLGN3 and PTTG1 mRNA in serum EVs from glioma patients (n=23) and healthy individuals (n=12). We evaluated the ability of EGFR + EVs to differentiate high-grade and low-grade glioma patients and checked the correlation between EGFR in EVs and the ki-67 labeling index (LI) in the tumor tissue. Results : We demonstrated that EGFR + EVs are effective diagnostic and prognostic markers of glioma. The expression of EGFR in serum EVs can accurately differentiate high-grade and low-grade glioma patients, and EGFR in EVs positively correlates with ki-67 LI in the tumor tissue. We also showed the potential of NLGN3 and PTTG1 mRNA in EVs for detecting glioma patients. Conclusions : We demonstrate that the protein expression of EGFR in serum EVs is an effective diagnostic marker of glioma. EGFR in EVs highly correlates with the malignancy of glioma. We also show the potential of NLGN3 and PTTG1 in EVs for detecting glioma. The optimized flow cytometry with the aid of microbead-based EV enrichment show its potential as a noninvasive method for the detection of glioma and will be beneficial to the management of glioma.

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Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

Cited by 7 publications

References 39 publications

Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway

Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway

miR‑24 regulates angiogenesis in gliomas

Evaluation of serum extracellular vesicles as noninvasive diagnostic markers of glioma

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