Expression In Glioma Tissues Research Articles

The tumorigenic effect of the high expression of ABRACL in glioma and its potential as a therapeutic target

Gliomas are the most common malignant intracranial tumors, with no effective treatments. Better understanding and identification of novel targets are urgently warranted. Actin-binding Rho activating C-terminal like (ABRACL) has been reported as an oncogene in several cancer types. However, the potential roles of ABRACL in the tumorigenesis of malignant glioma remain unknown. We discovered that ABRACL is highly expressed in different sub-types of gliomas in both CGGA and TCGA databases, which was further validated in glioblastoma cell lines and normal human astrocyte lines. RT-qPCR, Western blotting and immunohistochemistry demonstrated that ABRACL expression in glioma tissues was upregulated along with the increasing WHO grades. Further survival analysis of glioma patients also revealed that the overall survival of patients in the ABRACL high expression level group were significantly shorter than those in the low expression level group. Knockdown of ABRACL inhibited the proliferation, cell migration, invasion and cytodynamics behaviors in glioma cell lines via activating STAT3 signaling, which also induced apoptosis and cell cycle arrest. Conversely, overexpressing ABRACL promoted cell renewing and migration, enabled more flexible cell deformation, supporting ABRACL being a bona fide oncogene. Intracranial orthotopic xenograft experiment further confirmed that ABRACL downregulation significantly suppressed glioma growth. These results have demonstrated that the tumorigenic effect of ABRACL is partly mediated by STAT3, whose expression also correlates with clinical prognosis. ABRACL facilitates glioma malignancy phenotype through regulating the cytoskeleton by activating STAT3 pathway, suggesting that it may represent a potential therapeutic target for glioblastoma.

FERMT1 suppression induces anti-tumor effects and reduces stemness in glioma cancer cells

ObjectiveGlioma is a leading cause of mortality worldwide, its recurrence poses a major challenge in achieving effective treatment outcomes. Cancer stem cells (CSCs) have emerged as key contributors to tumor relapse and chemotherapy resistance, making them attractive targets for glioma cancer therapy. This study investigated the potential of FERMT1 as a prognostic biomarker and its role in regulating stemness through cell cycle in glioma.MethodsUsing data from TCGA-GBM, GSE4290, GSE50161 and GSE147352 for analysis of FERMT1 expression in glioma tissues. Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formation ability, invasion and migration were investigated. The influences of FERMT1 on expression of glycolysis-related proteins and levels of ATP, glucose, lactate and G6PDH were also explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced.ResultsSignificant upregulation of FERMT1 in glioma tissues was observed. Silencing FERMT1 not only affected the cell cycle but also led to a notable reduction in proliferation, invasion and migration. The expression of glycolysis-associated proteins including GLUT1, GLUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as well as decreased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover, FERMT1 knockdown significantly reduced sphere diameter, along with inhibiting the expression of transcription factors associated with stemness in glioma cells.ConclusionThese findings demonstrated that FERMT1 could be an ideal target for the advancement of innovative strategies against glioma treatment via modulating cellular process involved in stemness regulation and metabolism.

S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma

BackgroundS100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression. This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression. MethodsGlioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center. S100A8 expression in glioma tissues was analyzed using immunohistochemistry (IHC) to establish its correlation with clinicopathological features in patients. The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases. Then, we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell, wound healing, CCK8, and intracranial tumor models. Subsequently, bioinformatics analysis, single-cell sequencing and coimmunoprecipitation (Co-IP) were used to explore the underlying mechanism. ResultsS100A8 was upregulated in gliomas compared to paracancerous tissues, and this phenotype was significantly correlated with poor prognosis. Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma (HGG) group than that in the low-grade glioma (LGG) group. S100A8 overexpression in glioma cell lines promoted cell proliferation, migration and invasion, while silencing S100A8 reversed these effects. In vivo experiments, S100A8 knockdown can significantly reduce the tumor burden of glioma cells. Notably, S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4, which subsequently induced NF-κB signaling and IL-10 secretion within the tumor microenvironment. ConclusionsS100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma. S100A8 might represent a therapeutic target for further basic research or clinical management of glioma.

TRIM6 promotes glioma malignant progression by enhancing FOXO3A ubiquitination and degradation

PurposeTRIM6, an E3 ubiquitin ligase with tripartite motif, directly targets protein substrates for degradation through ubiquitination. Studies have shown that TRIM6 plays a significant role in tumor development in various human malignancies. Thus, the aim of this study was to investigate the importance of TRIM6 and its associated mechanism in promoting the progression of glioma. MethodsThe expression of TRIM6 and its prognostic value in glioma patients were collected from the TCGA and CGGA databases. The effects of TRIM6 on glioma were investigated in vitro by CCK8, colony formation, wound healing, and transwell assays. Co-IP and western blot analysis were used to detect the interaction between TRIM6 and FOXO3A. The effects of TRIM6 were verified in vivo in subcutaneously xenograft models, and tumor size, and immunohistochemical changes were observed. ResultsOur analysis of TRIM6 expression in glioma tissues revealed a high level of expression, and the heightened expression of TRIM6 showed a positive correlation with the unfavorable prognosis among glioma/GBM patients. Through loss-of-function and gain-of-function experiments, we observed a profound impact on the proliferation, invasion, and migration abilities of glioma cells both in vitro and in vivo upon deletion of TRIM6. Conversely, the overexpression of TRIM6 intensified the malignant characteristics of glioma. Additionally, our findings revealed a significant interaction between TRIM6 and FOXO3A, wherein TRIM6 contributed to the destabilization of FOXO3A protein by promoting its ubiquitination and subsequent degradation. Experiments conducted in the rescue study affirmed that the promotion of glioma cell proliferation, invasion, and migration is facilitated by TRIM6 through the suppression of FOXO3A protein levels. ConclusionsThese observations imply that the TRIM6-FOXO3A axis could potentially serve as an innovative focus for intervening in glioma.

HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments

BackgroundLaminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited.MethodsWe conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored.ResultsLAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion.ConclusionsHigh expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.

DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway

BackgroundGlioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated. MethodsThis study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored. ResultsOur study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway. ConclusionsPSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.

WSCD2 Expression: Its Relevance to Tumor-Infiltrating Immune Cells and Glioma Prognosis.

Patients with glioma have limited treatment options and experience poor prognoses. Therefore, it is urgently needed to explore new diagnostic and therapeutic targets. This study aimed to investigate the relevance of WSC domain-containing 2 (WSCD2) expression to glioma, clinicopathological characteristics, tumor-infiltrating immune cells (TILs), and patient prognosis. We analyzed WSCD2 mRNA expression in glioma tissues and patient survival using the Gene Expression Profiling Interactive Analysis database. Furthermore, the relationship between the expressions of WSCD2 mRNA and TILs in gliomas was evaluated utilizing the Tumor Immune Estimation Resource database. Lastly, we employed multiplex immunohistochemistry to detect the protein expressions of WSCD2 and TILs in glioma tissues. WSCD2 mRNA expression in glioma tissues was lower than that in tissues of benign brain disease. High WSCD2 mRNA expression was also significantly associated with a favorable outcome. Additionally, WSCD2 mRNA expression was correlated with TIL expression in glioma; however, no such relationship was detected between the protein expressions of WSCD2 and TILs in glioma tissues. Cox regression multivariate analysis and Kaplan-Meier survival analysis showed that WSCD2 expression in glioma tissues could be an independent prognostic factor. This study highlights the correlation between WSCD2 expression and TILs and demonstrates the prognostic significance of WSCD2 in glioma. Furthermore, our results suggest that WSCD2 may be a potential immunotherapy target in glioma.

Basic Transcription Factor 3 Like 4 Enhances Malignant Phenotypes through Modulating Tumor Cell Function and Immune Microenvironment in Glioma

Recent investigations into the tumor microenvironment have provided insights into the limited response of glioma progression to immunotherapy. However, the specific involvement of Basic Transcription Factor 3 Like 4 (BTF3L4) in glioma progression and its correlation with immune cell infiltration remained areas of uncertainty that require further exploration. In the present study, BTF3L4 expression was delineated using gene-expression-profiling-interactive-analysis and multiplex-immunohistological staining of tissue microarrays. Then, the prognostic value of BTF3L4 was assessed using Cox regression models and Kaplan-Meier methods and conducted in vitro experiments to investigate how BTF3L4 protein impacts the proliferation, migration, and invasion capabilities of glioma cells. Furthermore, the Cibersort and Estimate methods were employed to quantify immune cells that correlate to BTF3L4 expression and applied multiplex-immunohistological staining to investigate its correlation with infiltrated immune cells in glioma tissues. These findings revealed a higher BTF3L4 expression in glioma tissues compared to non-tumor brain tissues, which correlated with clinical characteristics and worse patient prognosis. Furthermore, the downregulation of BTF3L4 protein in glioma cell line had a detrimental effect on cell migration, invasion, and proliferation. Additionally, the association between BTF3L4 and key immune molecules in glioma, particularly with the infiltration of CD66B+ neutrophils and PD-L1 expression was identified. These results highlight the prognostic significance of BTF3L4 and propose BTF3L4 as a potential target for glioma immune therapy.

PVT1 promotes proliferation and macrophage immunosuppressive polarization through STAT1 and CX3CL1 regulation in glioblastoma multiforme.

This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA, in glioblastoma multiforme (GBM) and its impact on the tumor microenvironment (TME). We assessed aberrant PVT1 expression in glioma tissues and its impact on GBM cell growth invitro and invivo. Additionally, we investigated PVT1's role in influencing glioma-associated macrophages. To understand PVT1's role in cell growth and the immunosuppressive TME, we performed a series of comprehensive experiments. PVT1 was overexpressed in GBM due to copy number amplification, correlating with poor prognosis. Elevated PVT1 promoted GBM cell proliferation, while its downregulation inhibited growth invitro and invivo. PVT1 inhibited type I interferon-stimulated genes (ISGs), with STAT1 as the central hub. PVT1 correlated with macrophage enrichment and regulated CX3CL1 expression, promoting recruitment and M2 phenotype polarization of macrophages. PVT1 localized to the cell nucleus and bound to DHX9, enriching at the promoter regions of STAT1 and CX3CL1, modulating ISGs and CX3CL1 expression. PVT1 plays a significant role in GBM, correlating with poor prognosis, promoting cell growth, and shaping an immunosuppressive TME via STAT1 and CX3CL1 regulation. Targeting PVT1 may hold therapeutic promise for GBM patients.

Identification and Validation of TEAD Family’s Prognostic Effects and Immune Microenvironment Regulations in Glioma

Background. Gliomas are primary malignant tumors of the central nervous system. The TEA domain transcription factor (TEAD) family proteins are the ultimate effector molecules of the Hippo pathway. However, their expression and function in gliomas have not been further studied. Methods. This study employed R software as the primary analysis tool. Public databases were used to analyze the expression and prognostic significance of TEADs. Functional enrichment analyses were conducted to determine the functions of the TEADs. We then explored their interaction with tumor‐infiltrating immune cells and immune checkpoint proteins (ICPs). A Cox regression model was used to estimate the prognostic value of the TEADs. Finally, we conducted experiments to confirm TEAD3’s function in vitro. Results. TEAD expression was frequently increased in glioma and other malignant tumors. High TEAD expression was found to be substantially linked with isocitrate dehydrogenase (IDH) wild type, noncodeletion of 1p/19q, high WHO grade, and poor prognosis in glioma patients. Functional analyses revealed TEAD involvement in cancer cell transcription. The high expression of TEADs was greatly related to the myeloid‐derived suppressor cells (MDSCs) and regulatory T‐cells (Tregs) infiltration. TEADs also showed significant correlations with ICP expression in glioma tissues. The Cox regression model demonstrated significant diagnostic and prognostic efficacy in glioma patients. The reduction in TEAD3 affects tumor cell proliferation, migration, invasion, and immune regulation. RNA sequencing disclosed that TEAD3 regulates immune‐related pathways, including negative regulation of the CTLA4 inhibitory pathway. Higher TEAD3 expression portended shorter overall survival (OS) and disease‐free survival (DFS) in patients with gliomas based on clinical samples. Conclusions. TEADs are overexpressed in gliomas and are associated with a poor prognosis. Importantly, this study discovered that TEADs influence the immunological milieu of glioma by modulating genes associated with immune infiltration.

AQP1 as a novel biomarker to predict prognosis and tumor immunity in glioma patients

Abstract Background Glioma is a kind of nervous system cancer with a low overall survival rate. Aquaporin 1 (AQP1) is linked to a number of cancers. Its prognostic relevance and immunological consequences in gliomas, however, are unclear. Objectives Our objective was to thoroughly examine the modified expression of AQP1, its prognostic significance, and its correlation with immune cells and markers to discover innovative molecular immunotherapy strategies for glioma patients. Methods RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used. In addition, we used real-time reverse transcription polymerase chain reaction (RT-PCR) and Western Blot methods to monitor AQP1 expression in glioma tissues. Results AQP1 expression was greater in gliomas than in traumatized brain tissues. The increased AQP1 expression in gliomas was additionally confirmed through immunohistochemical analysis in the Human Protein Atlas (HPA) repository. An elevated level of AQP1 expression was identified as a separate determinant of the overall survival (OS) and prognosis of individuals with glioma. AQP1 expression was shown to be tightly linked to the tumor immune milieu, immune checkpoint blockade (ICB) and temozolomide drug reaction. In conclusion, the 50 genes that show coexpression with AQP1 indicate that the predominant functions and pathways are related to anterior pattern specification, pattern specification, regionalization, high-density lipoprotein particles, protein–lipid complexes, glycosaminoglycan binding, DNA-binding transcription repressor specific activation to RNA polymerase II, DNA-binding transcription repressor activity, nitrogen metabolism, alpha-linolenic acid metabolism, and fat digestion and absorption. Conclusions The results indicate that AQP1 could serve as both a predictive marker and a potential treatment target in glioma.

The Clinical Relevance and Functional Implications of Thymosin Beta-10 in Glioma.

Glioma is a highly aggressive form of brain cancer characterized by limited treatment options and poor patient prognosis. In this study, we aimed to elucidate the oncogenic role of thymosin beta-10 (TMSB10) in glioma through comprehensive analyses of patient data from the TCGA and GTEx databases. Our investigation encompassed several key aspects, including the analysis of patients' clinical characteristics, survival analysis, in vitro and in vivo functional experiments, and the exploration of correlations between TMSB10 expression and immune cell infiltration. Our findings revealed a significant upregulation of TMSB10 expression in glioma tissues compared to normal brain tissues, with higher expression levels observed in tumors of advanced histological grades. Moreover, we observed positive correlations between TMSB10 expression and patient age, while no significant association with gender was detected. Additionally, TMSB10 exhibited marked elevation in gliomas with wild-type IDH and noncodeletion of 1p/19q. Survival analysis indicated that high TMSB10 expression was significantly associated with worse overall survival, disease-specific survival, and progression-free survival in glioma patients. Functionally, knockdown of TMSB10 in glioma cells resulted in reduced cellular growth rates and impaired tumor growth in xenograft models. Furthermore, our study revealed intriguing correlations between TMSB10 expression and immune cell infiltration within the tumor microenvironment. Specifically, TMSB10 showed negative associations with plasmacytoid dendritic cells (pDC) and γδ T cells (Tgd), while displaying positive correlations with neutrophils and macrophages. These findings collectively provide valuable insights into the oncogenic properties of TMSB10 in glioma, suggesting its potential as a therapeutic target and a biomarker for patient stratification.

PLEKHA4 promotes glioblastoma progression through apoptosis inhibition, tumor cell migration, and macrophage infiltration

BackgroundGlioblastoma(GBM) has a profound impact on human health, making the identification of reliable prognostic biomarkers pivotal. While PLEKHA4 has been associated with tumor genesis and development, its role in gliomas is still uncertain. MethodsWe analyzed PLEKHA4 expression in tumor tissues using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we utilized TCGA data to investigate its impact on prognosis, pathway enrichment, and immune infiltration. In vitro loss-of-function experiments were conducted to elucidate the effect of PLEKHA4 silencing on GBM cell behavior. ResultsTCGA and GEO data sets revealed increased levels of PLEKHA4 expression in glioma tissues. Furthermore, we identified a correlation between PLEKHA4 expression and higher disease classification, pathological grading, and poorer prognosis. Silencing PLEKHA4 in vitro resulted in decreased glioma cell migration and increased apoptosis. It also reduced macrophage infiltration and hindered M2 polarization of macrophages. ConclusionOur findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.

PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas.

Glioma is the most common intracranial malignancy. Immune-infiltration and tumour stemness are associated with the prognosis of glioma. Although pleckstrin homology containing family A, number 4 (PLEKHA4) is widely expressed in various human cancers, its role in glioma remains unclear. We examined the features and clinical significance of PLEKHA4 in gliomas by analysing relevant data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was performed to determine the possible functions and pathways involving PLEKHA4 in glioma. The relationship between PLEKHA4 expression and the degree of oncogenic dedifferentiation was analysed using stemness scores (ss) calculated from epigenetic and transcriptomic features. We also explored the relationship between PLEKHA4 expression and immune cell infiltration in gliomas using the CIBERSORT databases. Furthermore, drug sensitivity analysis was performed using datasets from the GDSC and GTRP databases. In addition, we performed relevant in vitro experimental studies. PLEKHA4 DNA hypomethylation status was associated with its high expression in glioma tissues as well as poor prognoses. Univariate and multivariate Cox analyses indicated that PLEKHA4 expression may be considered as an independent prognostic factor in patients with glioma. GSEA indicated that high PLEKHA4 expression was associated with Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless-Type MMTV Integration Site Family (Wnt), JUN N-terminal kinase (JNK) signalling pathways and involved in apoptotic, cytoskeletal, and cell adhesion biological processes (BPs). In addition, increased PLEKHA4 expression was associated with higher glioma stemness scores than lower PLEKHA4 expression levels. Furthermore, the expression of PLEKHA4 was shown to be associated with glioma infiltration by CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Drug sensitivity analysis also showed that PLEKHA4 expression was negatively correlated with the sensitivity of several small molecule kinase inhibitors. Furthermore, in vitro experiments confirmed that PLEKHA4 knockdown inhibited the proliferation of glioma cells. PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma.

Hsa_circ_0010889 downregulation inhibits malignant glioma progression by modulating the miR-590-5p/SATB1 axis.

Glioma is a general neurological tumor and circular RNAs (circRNAs) have been implicated in glioma development. However, the underlying mechanisms and circRNA biological functions responsible for the regulation of glioma progression remain unknown. In this study, we employ next-generation sequencing (NGS) to investigate altered circRNA expression in glioma tissues. Regulatory mechanisms were studied using luciferase reporter analyses, transwell migration, CCK8, and EdU analysis. Tumorigenesis and metastasis assays were utilized to determine the function of hsa_circ_0010889 in glioma. Our results showed that hsa_circ_0010889 expression increased in glioma cell lines and tissues, indicating that hsa_circ_0010889 may be involved in glioma progression. Downregulation of hsa_circ_0010889 inhibited glioma invasion and proliferation in both in vitro and in vivo experiments and luciferase report assays found that miR-590-5p and SATB1 were downstream targets for hsa_circ_0010889. SATB1 overexpression or miR-590-5p inhibition reversed glioma cells proliferation and migration post-silencing of hsa_circ_0010889. Taken together, our study demonstrates that hsa_circ_0010889 downregulation inhibits glioma progression through the miR-590-5p/SATB1 axis.

The overexpression and clinical significance of TBX15 in human gliomas

T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.

Down-Regulation of CEND1 Expression Contributes to The Progression and Temozolomide Resistance of Glioma.

This study was conducted to clarify the expression characteristics of cell cycle exit and neuronal differentiation 1 (CEND1) in glioma and its effects on the proliferation, migration, invasion, and resistance to temozolomide (TMZ) of glioma cells. In this experimental study, CEND1 expression in glioma tissues and its relationship with patients' survival were analyzed through bioinformatics. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to detect CEND1 expression in glioma tissues. The cell counting kit-8 (CCK-8) method was adopted to detect cell viability and the effects of different concentrations of TMZ on the inhibition rate of glioma cell proliferation, and the median inhibitory concentration of TMZ (IC50 value) was calculated. 5-Bromo- 2'-deoxyuridine (BrdU), wound healing and Transwell assays were performed to evaluate the impacts of CEND1 on glioma cell proliferation, migration, and invasion. Besides, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and Gene Set Enrichment Analysis (GSEA) were applied to predict the pathways regulated by CEND1. Nuclear factor-kappa B p65 (NF-κB p65) and phospho-p65 (p-p65) expression were detected by Western blot. CEND1 expression was reduced in glioma tissues and cells, and its low expression was significantly associated with the shorter survival of glioma patients. CEND1 knockdown promoted glioma cell growth, migration, and invasion, and increased the IC50 value of TMZ, whereas up-regulating CEND1 expression worked oppositely. Genes co-expressed with CEND1 were enriched in the NF-κB pathway, and knocking down CEND1 facilitated p-p65 expression, while CEND1 overexpression suppressed p-p65 expression. CEND1 inhibits glioma cell proliferation, migration, invasion, and resistance to TMZ by inhibiting the NF- κB pathway.

Deciphering the role of QPCTL in glioma progression and cancer immunotherapy.

Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy. QPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors. In contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p < 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p < 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness. High QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.

Interleukin 37 inhibits the migration and invasion of Glioma cells

ABSTRACT Glioma is a medical term that describes a tumor originating in the brain. Several risk factors could develop glioma such as occupational exposure, gene mutation and ionizing radiation. Therefore, we aim to determine the expression and biological function of interleukin 37 (IL-37) in gliomas with different pathological grades. We used 95 participants with different pathological grades of glioma as our data subjects. We used CCK-8 assay and transwell assay to explore the proliferation of U251 over-expressing IL-37 and migration and invasion of U251. We found that IL-37 expression in tumor tissues was significantly higher than in normal tissue. The reduced IL-37 expression in gliomas was significantly associated with a higher WHO grade and lower Karnofsky Performance Status score. IL-37 expression in glioma tissues showed a decline with the increase of the WHO glioma grade. Patients with low IL-37 expression showed a shorter median survival. Transwell assay indicated that migration and invasion of U251 over-expressing IL-37 was significantly lower than that of the control at 24 h. Our findings showed that low IL-37 expression was negatively correlated with pathological grade and was positively correlated with survival time.