scholarly journals Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas

2018 ◽  
Vol 19 (11) ◽  
pp. 3353 ◽  
Author(s):  
Yi-Hsuan Chen ◽  
Dueng-Yuan Hueng ◽  
Wen-Chiuan Tsai
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Proteolipid Protein ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Human Gliomas ◽  
Advanced Tumor ◽  
Glioma Cell Lines ◽  
Aggressive Tumor

Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior.

scholarly journals Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

2018 ◽  
Vol 46 (3) ◽  
pp. 1055-1064 ◽  
Author(s):  
Xin Chen ◽  
Deheng Li ◽  
Yang Gao ◽  
Wei Tang ◽  
Lao IW ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Glioma Cell Lines ◽  
Glioma Cell Proliferation ◽  
Proliferation And Invasion

Background/Aims: Long noncoding RNAs (lncRNAs) are a novel class of protein-noncoding transcripts that are aberrantly expressed in multiple diseases including cancers. LINC00152 has been identified as an oncogene involved in many kinds of cancer; however, its expression pattern and function in human glioma remain unclear. Methods: Quantitative real-time polymerase chain reaction was carried out to measure LINC00152 expression in human glioma cell lines and tissues. CCK-8 and EdU assays were performed to assess cell proliferation, and scratch assays and Transwell assays were used to assess cell migration and invasion, respectively. Luciferase reporter assays were carried out to determine the interaction between miR-16 and LINC00152. In vivo experiments were conducted to assess tumor formation. Results: LINC00152 was found to be significantly upregulated in human glioma cell lines and clinical samples. Knockdown of LINC00152 suppressed glioma cell proliferation, migration, and invasion in vitro. In vivo assays in nude mice confirmed that LINC00152 knockdown inhibits tumor growth. Furthermore, mechanistic investigation showed that LINC00152 binds to miR-16 in a sequence-specific manner and suppresses its expression. miR-16 inhibition strongly attenuated LINC00152 knockdown–mediated suppressive effects on proliferation, migration, and invasion. Moreover, LINC00152 induced BMI1 expression by sponging miR-16; this effect further promoted glioma cell proliferation and invasion. Conclusion: We regard LINC00152 as an oncogenic lncRNA promoting glioma cell proliferation and invasion and as a potential target for human glioma treatment.

scholarly journals Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 492 ◽  
Author(s):  
Weder Pereira de Menezes ◽  
Viviane Aline Oliveira Silva ◽  
Izabela Natália Faria Gomes ◽  
Marcela Nunes Rosa ◽  
Maria Luisa Corcoll Spina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
In Silico ◽  
Glioma Cell ◽  
Clinicopathological Features ◽  
Migration And Invasion ◽  
High Grade ◽  
Methylthioadenosine Phosphorylase ◽  
Frequent Event ◽  
High Grade Gliomas

The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

scholarly journals LncRNA-XIST interacts with miR-29c to modulate the chemoresistance of glioma cell to TMZ through DNA mismatch repair pathway

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Peng Du ◽  
Haiting Zhao ◽  
Renjun Peng ◽  
Qing Liu ◽  
Jian Yuan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mismatch Repair ◽  
Cell Lines ◽  
Glioma Cell ◽  
Dna Mismatch Repair ◽  
Tumor Biology ◽  
Glioma Cells ◽  
Dna Mismatch ◽  
Cell Proliferation Inhibition ◽  
Glioma Cell Lines

Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However, growing resistance to TMZ remains a major challenge for clinicians. Recent evidence emphasizes the key regulatory roles of non-coding RNAs (lncRNAs and miRNAs) in tumor biology, including the chemoresistance of cancers. However, little is known about the role and regulation mechanisms of lncRNA cancer X-inactive specific transcripts (XIST) in glioma tumorigenesis and chemotherapy resistance. In the present study, higher XIST expression was observed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. XIST knockdown alone was sufficient to inhibit glioma cell proliferation and to amplify TMZ-induced cell proliferation inhibition. Moreover, XIST knockdown can sensitize TMZ-resistant glioma cells to TMZ. XIST can inhibit miR-29c expression by directly targetting TMZ-resistant glioma cells. DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays a key role in TMZ resistance; transcription factor specificity protein 1 (SP1), a regulator of DNA mismatch repair (MMR) key protein MSH6, has been reported to be up-regulated in TMZ-resistant glioma cell lines. In the present study, we show that XIST/miR-29c coregulates SP1 and MGMT expression in TMZ-resistant glioma cell lines. Our data suggest that XIST can amplify the chemoresistance of glioma cell lines to TMZ through directly targetting miR-29c via SP1 and MGMT. XIST/miR-29c may be a potential therapeutic target for glioma treatment.

scholarly journals CBMT-18. THE ROLE OF BIOMARKER CANDIDATE GELSOLIN AND ITS MICRORNAS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi36-vi37
Author(s):  
Mitsutoshi Nakada ◽  
Jiakang Zhang ◽  
Taskuya Furuta ◽  
Shabierjiang Jiapaer ◽  
Sho Tamai ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glycogen Synthase ◽  
Inverse Correlation ◽  
Progression Free Survival ◽  
Expression Level ◽  
Normal Brain ◽  
Kaplan Meier ◽  
Glioma Cell Lines ◽  
Proliferation And Invasion

Abstract BACKGROUND Among potential glioblastoma (GBM) blood biomarkers that we identified recently, we focused on gelsolin (GSN), a key regulator of actin filament disassembly. GSN was significantly lower in the blood of patients with GBM than in that of healthy controls. In this study, we analyzed the function of GSN and identified microRNAs (miRs) involved in GSN expression in GBM. METHODS QRT-PCR and western blot were introduced to evaluate the expression level of GSN in normal brain and GBM tissue. The localization of GSN was examined by immunohistochemistry and immunocytochemistry using human samples. The association between the expression level of GSN and progression free survival (PFS) /overall survival (OS) in GBM was assessed by Kaplan-Meier analysis. The function of GSN and its signal transduction in glioma cell lines were analyzed using small interfering RNA (siRNA) knockdown of GSN. Additionally, miRs controlling GSN expression were retrieved from databases of miRs, and miRs related to GSN expression were identified in GBM tissues. RESULTS The expression level of GSN was significantly lower in GBM tissues compared to normal brains. Normal astrocytes mainly expressed GSN. High expressor of GSN showed longer PFS and OS than low expressor. Proliferation and invasion in glioma cell lines were significantly promoted by siRNA for GSN accompanied with the activation of glycogen synthase kinase 3β. In GBM tissues, the expression levels of GSN and miR-654-5p, 450b-5p showed an inverse correlation. The inhibitor for miR-654-5p and miR-450b-5p accelerated GSN expression resulting reduction of proliferation. CONCLUSION GSN plays a role as suppressor of proliferation and invasion in GBM. miR-654-5p and miR-450b-5p which control GSN expression can be targets against GBM.

Differential effects of vincristine and phenytoin on the proliferation, migration, and invasion of human glioma cell lines

1995 ◽  
Vol 82 (6) ◽  
pp. 1035-1043 ◽  
Author(s):  
Jörg-Christian Tonn ◽  
Hans Kristian Haugland ◽  
Jaakko Saraste ◽  
Klaus Roosen ◽  
Ole Didrik Laerum
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Dose Dependent ◽  
Fine Print

✓ The aim of this study was to investigate the antimigratory and antiinvasive potential of vincristine sulfate (VCR) on human glioma cells and to analyze whether phenytoin (5,5-diphenylhydantoin; DPH) might act synergistically with VCR. Vincristine affects the cytoplasmic microtubules; DPH has been reported to enhance VCR cytotoxicity in murine cells. In two human glioma cell lines, GaMG and D-37MG, we found VCR to reduce monolayer growth and colony formation in a dose-dependent fashion at concentrations of 10 ng/ml and above. Phenytoin increased the cytotoxic and cystostatic effects of VCR in monolayer cells but not in spheroids. Multicellular spheroids were used to investigate directional migration. A coculture system of GaMG and D-37MG spheroids with fetal rat brain aggregates was used to analyze and quantify tumor cell invasion. A dose-dependent inhibition of migration and invasion by VCR was observed in both cell lines without further enhancement by DPH. Immunofluorescence microscopy with antibodies against α-tubulin revealed dose-dependent morphological alterations in the microtubules when the cells were exposed to VCR but not after incubation with DPH. Based on the combination of standardized in vitro model systems currently in use and the present data, the authors strongly suggest that VCR inhibits migration and invasion of human glioma cells. This is not altered by DPH, which inhibits cell proliferation in combination with VCR.

scholarly journals A Novel Gene RNF138 Expressed in Human Gliomas and Its Function in the Glioma Cell Line U251

2012 ◽  
Vol 35 (3) ◽  
pp. 167-178 ◽  
Author(s):  
You-xin Zhou ◽  
San-song Chen ◽  
Ting-feng Wu ◽  
Da-dong Ding ◽  
Xiong-hui Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Brain Tissue ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
Glioma Tissue ◽  
Glioma Cell Lines

Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes and the inactivation of tumor suppressor genes. Whether the RING finger protein, RNF138, a newly discovered protein, plays a role in glioma oncogenesis is unknown. The present study investigates the expression levels of RNF138 mRNA in glioma samples and noncancerous brain samples and its function in the human glioma cell line U251.Methods: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of 35 pathological confirmed glioma samples (Grade I – 4 cases, Grade II – 13 cases, Grade III – 11 cases, and Grade IV – 7 cases) and five noncancerous brain tissue samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi) with the lentivirus vector system, the expression of RNF138 was inhibited in the human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138-knockdown on cell proliferation were assessed by Cellomics, and cell cycle and cell apoptosis were assessed by FACS.Results: The RNF138 mRNA is expressed in the five glioma cell lines, and its expression level is significantly higher in glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138 expression, U251 cell proliferation was inhibited and cell apoptosis increased. At the same time, S stage cells lessened and G2 stage cells increased.Conclusion: The RNF138 gene is highly expressed in glioma tissue and glioma cell lines. It plays an important role in glioma cell proliferation, apoptosis, and cell cycle.

scholarly journals TMEM60 Promotes the Proliferation and Migration and Inhibits the Apoptosis of Glioma through Modulating AKT Signaling

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Jingwen Wu ◽  
Xinghua Tang ◽  
Xuejuan Yu ◽  
Xiaoli Zhang ◽  
Wenjun Yang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Glioma Cell Lines

Glioma is a highly fatal malignancy with aggressive proliferation, migration, and invasion metastasis due to aberrant genetic regulation. This work aimed to determine the function of transmembrane protein 60 (TMEM60) during glioma development. The level of TMEM60 in glioma tissues and normal tissues and its correlation with glioma prognosis were checked in The Cancer Genome Atlas (TCGA) database. The levels of TMEM60 in glioma cell lines and normal astrocytes were determined by quantitative real-time PCR and western blotting assay. TMEM60 knockdown and overexpression were conducted, followed by detection of cell viability, migration, invasion, and apoptosis. CCK-8 and colony formation assay were adopted to detect cell viability proliferation. Transwell assay was performed to measure cell migration and invasion. Cell apoptosis was evaluated by flow cytometry. The alternation of key proteins in the PI3K/Akt signaling pathway was measured by western blotting. TMEM60 expression was significantly higher in glioma tissues than that in the healthy control and was correlated with poor overall survival of patients. The protein and mRNA levels of TMEM60 were both elevated in glioma cell lines in comparison with the normal cell lines. Elevated level of TMEM60 led to enhanced proliferation, migration, and invasion and suppressed cell apoptosis. TMEM60 promoted the activation of PI3K/Akt signaling. Our data suggested that TMEM60 plays an oncogenic role in glioma progression via activating the PI3K/Akt signaling pathway.

Molecular determinants of glioma cell migration and invasion

2001 ◽  
Vol 94 (6) ◽  
pp. 978-984 ◽  
Author(s):  
Christine Wild-Bode ◽  
Michael Weller ◽  
Wolfgang Wick
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Growth Patterns ◽  
Migration And Invasion ◽  
Integrin Expression ◽  
Content Type ◽  
Expression Levels ◽  
Glioma Cell Lines ◽  
Fine Print

Object. Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality. Methods. The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with αVβ3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines. Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of αVβ3 integrin did not predict migration or invasion, a neutralizing αVβ3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of αVβ3 integrin expression, thus indicating the important role of αVβ3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines. Conclusions. Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The αVβ3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on αVβ3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.

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