Levels In Glioma Tissues Research Articles

CircVCAN promotes glioma progression through the miR-488-3p/MEF2C-JAGGED1 axis.

Gliomas are the most prevalent primary malignant brain tumors worldwide. Growing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumors. We aimed to investigate the role and mechanism of circVCAN in glioma. RNase R treatment was utilized to assess the cyclic properties of circVCAN. CircVCAN, miR-488-3p, and myocyte enhancer factor 2C (MEF2C) levels in glioma tissues and cells were detected by reverse transcription real-time polymerase chain reaction (RT-qPCR), and the localization of them in glioma cells was determined with fluorescence in situ hybridization. Furthermore, a variety of biologically functional assessments were used to validate the role of circVCAN in glioma. The regulatory mechanisms of circVCAN, miR-488-3p, and MEF2C were further confirmed by double luciferase reporter gene assay, RNA immunoprecipitation and RNA pull-down assay, and the binding of MEF2C to JAGGED1 was revealed by chromatin immunoprecipitation. Additionally, a xenograft tumor model was constructed to demonstrate the effect of circVCAN on tumor growth in vivo. Our results indicated that circVCAN was more stable than its linear RNA and was significantly upregulated in gliomas. CircVCAN overexpression stimulated glioma cells to proliferate and metastasize, but circVCAN silencing exerted the opposite effect. Meanwhile, silencing circVCAN inhibited tumor growth in vivo. Moreover, we found that circVCAN interacted with miR-488-3p to regulate MEF2C expression, and miR-488-3p inhibition or MEF2C overexpression reversed the inhibitory effect on malignant bio-behaviors mediated by circVCAN knockdown in glioma cells. MEF2C promoted the transcription of JAGGED1, and circVCAN knockdown reduced the binding between MEF2C and JAGGED1. Collectively, circVCAN is a carcinogenic circRNA in glioma, and the circVCAN/miR-488-3p/MEF2C-JAGGED1 axis could serve as a potential target for the management of glioma.

Prognostic value and drug sensitivity of F‑box and leucine‑rich repeat protein 6 in glioma.

Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich repeat protein 6 (FBXL6), a protein crucial for the cell cycle and tumorigenesis, is highly expressed in certain types of tumors. The high expression level of FBXL6 is reported to promote tumor growth and adversely affect patient survival. However, the molecular mechanism, prognostic value and drug sensitivity of FBXL6 in glioma remain unclear. To address this, the present study analyzed FBXL6 expression in gliomas, utilizing data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Analysis of FBXL6 mRNA expression levels, combined with patient factors such as age, sex and tumor grade using Kaplan-Meier plots and nomograms, demonstrated a strong correlation between FBXL6 expression and glioma progression. Co-expression networks provided further insights into the biological function of FBXL6. Additionally, using CIBERSORT and TISDB tools, the correlation between FBXL6 expression correlation tumor-infiltrating immune cells and immune genes was demonstrated to be statistically significant. These findings were validated by examining FBXL6 mRNA and protein levels in glioma tissues using various techniques, including western blot, reverse transcription-quantitative PCR and immunohistochemistry. These assays demonstrated the role of FBXL6 in glioma progression. Furthermore, drug sensitivity analysis demonstrated a strong correlation between FBXL6 expression and various drugs, which indicated that FBXL6 may potentially act as a future promising therapeutic target in glioma treatment. Therefore, the present study identified FBXL6 as a diagnostic and prognostic marker in patients with gliomas and highlighted its potential role in glioma progression.

Transmembrane and Ubiquitin-Like Domain-Containing 1 Promotes Glioma Growth and Indicates Unfavorable Prognosis.

Ubiquitin-related proteins have garnered increasing attention for their roles in tumorigenesis. Transmembrane and ubiquitin-like domain-containing 1 (TMUB1) is a recently discovered protein in the ubiquitin-like domain family, yet its involvement in glioma remains poorly understood. This study is aimed at investigating the functional significance and clinical relevance of TMUB1 in glioma. We conducted a comprehensive analysis using two cohorts: a retrospective glioma cohort from our hospital and The Cancer Genome Atlas (TCGA) cohort. The mRNA levels of TMUB1 were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical associations of TMUB1 in these cohorts were evaluated using correlation tests, chi-square tests, and survival analyses. Additionally, we performed TMUB1 knockdown in U87 and LN-229 human glioma cell lines, and cellular growth was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Our results revealed that TMUB1 expression was elevated in glioma tissues compared to normal brain tissues. Notably, lower TMUB1 expression correlated with favorable characteristics such as lower World Health Organization (WHO) grade and 1p/19q codeletion. Moreover, patients with higher TMUB1 levels in glioma tissues exhibited worse prognosis in both TCGA cohort and our retrospective cohort, underscoring its prognostic significance in gliomas. Cellular experiments demonstrated that TMUB1 silencing suppressed the growth of glioma cells. TMUB1 emerges as a novel and clinically relevant prognostic biomarker for gliomas. Targeting TMUB1 holds promise as a potential strategy for glioma treatment. This study contributes valuable insights into the multifaceted role of TMUB1 in glioma pathogenesis and its potential as a diagnostic and therapeutic target.

BTN2A2, a new biomarker and therapeutic target for glioma.

Protein casein 2A2 (BTN2A2) is a costimulatory molecule first identified in antigen-presenting cells. Studies have shown the involvement of BTN2A2 in immunity. However, the exact role and the mechanism of BTN2A2 in tumors are still unclear. First, we performed real-time PCR to measure BTN2A2 expression in glioma cell lines. Next, we performed Genes Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to understand the mechanism of BTN2A2 in glioma. Next, we used the "ESTIMATE", "ssGSEA" and "CIBERSORT" algorithms to analyze the correlation between BTN2A2 and immune cell infiltration (ICI). Finally, we performed immunohistochemistry, growth curve, transwell, and colony formation assays to determine the functions of BTN2A2 in glioma. Our results showed an increase in BTN2A2 expression levels in glioma tissues and cells. Next, we determined that BTN2A2 was correlated with the prognosis of patients with glioma. Then, using the ESTIMATE, ssGSEA, and CIBERSORT algorithms, we discovered that BTN2A2 was significantly associated with immune cell infiltration (ICI) in glioma. We observed an increase in BTN2A2 expression levels with an increase in the patient's tumor grade. Furthermore, BTN2A2 significantly enhanced the proliferative and migratory abilities of glioma cells. Our results showed a significant increase in BTN2A2 expression levels in glioma cells and tissues. Furthermore, the prognosis of patients expressing high BTN2A2 levels was poor. Moreover, BTN2A2 was correlated with progression and ICI in patients with glioma. Together, this indicates that BTN2A2 could be a therapeutic target for patients with glioma.

Structuring and validating a prognostic model for low-grade gliomas based on the genes for plasma membrane tension.

Recent studies indicate that cell mechanics are associated with malignancy through its impact on cell migration and adhesion. Gliomas are the most common primary malignant brain tumors. Low-grade gliomas (LGGs) include diffuse LGGs (WHO grade II) and intermediate-grade gliomas (WHO grade III). Few studies have focused on membrane tension in LGGs. Herein, we assessed the prognostic value of plasma membrane tension-related genes (MTRGs) in LGGs. We selected plasma MTRGs identified in previous studies for analysis. Based on LGG RNA sequencing (RNA-seq) data in The Cancer Genome Atlas, a prognostic signature containing four genes was constructed via log-rank testing, LASSO regression and stepwise multivariate Cox regression and was validated with other datasets. Additionally, functional annotation, pathway enrichment and immune and molecular characteristics of the prognostic model defined subgroups were analyzed. Thereafter, a predictive nomogram that integrated baseline characteristics was constructed to determine the 3, 5, and 10-year overall survival (OS) of patients with LGG. Differentially expressed genes were confirmed via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Our MTRG prognostic signature was based on ARFIP2, PICK1, SH3GL2, and SRGAP3 expression levels. The high-risk group was more positively associated with apoptosis and cell adhesion pathways and exhibited a low IDH1 mutation rate, high TP53 mutation rate and a low 1p19q co-deletion rate. The high-risk group also exhibited incremental infiltration of immune cells, more forceful immune activities and high expression of immune checkpoints as well as benefited less from immune therapy compared with the low-risk group. Our prognostic model had better forecasting ability than other scoring systems. We found that the nomogram was a better tool for predicting outcomes for patients with LGG. Finally, qRT-PCR confirmed that SH3GL2 and SRGAP3 expression levels in glioma tissues were significantly lower than those in normal brain tissues. The results of IHC analysis confirmed that SH3GL2 protein expression was higher in patients with longer survival. Our plasma membrane tension-related gene prognostic signature is a prospective tool that can differentiate between prognosis, gene mutation landscape, immune microenvironment, immune infiltration and immunotherapeutic efficacy in LGG.

Characterization of aging cancer-associated fibroblasts draws implications in prognosis and immunotherapy response in low-grade gliomas

Background: Due to the highly variable prognosis of low-grade gliomas (LGGs), it is important to find robust biomarkers for predicting clinical outcomes. Aging cancer-associated fibroblasts (CAFs) within the senescent stroma of a tumor microenvironment (TME) have been recently reported to play a key role in tumor development. However, there are few studies focusing on this topic in gliomas. Methods and Results: Based on the transcriptome data from TCGA and CGGA databases, we identified aging CAF-related genes (ACAFRGs) in LGGs by the weighted gene co-expression network analysis (WGCNA) method, followed by which LGG samples were classified into two aging CAF-related gene clusters with distinct prognosis and characteristics of the TME. Machine learning algorithms were used to screen out eight featured ACAFRGs to characterize two aging CAF-related gene clusters, and a nomogram model was constructed to predict the probability of gene cluster A for each LGG sample. Then, a powerful aging CAF scoring system was developed to predict the prognosis and response to immune checkpoint blockage therapy. Finally, the ACAFRGs were verified in two glioma-related external datasets. The performance of the aging CAF score in predicting the immunotherapy response was further validated in two independent cohorts. We also confirmed the expression of ACAFRGs at the protein level in glioma tissues through the Human Protein Atlas website and Western blotting analysis. Conclusion: We developed a robust aging CAF scoring system to predict the prognosis and immunotherapy response in LGGs. Our findings may provide new targets for therapeutics and contribute to the exploration focusing on aging CAFs.

PTBP3 promotes tumorigenesis of glioblastoma by stabilizing Twist1

ObjectiveGlioblastoma (GBM) is the most common malignancy tumor of central nervous system. PTBP3 was closely associated with the development of tumor. However, the function and molecular mechanism of PTBP3 in GBM is little known. MethodsqPCR and immunoblotting were used to detect PTBP3 expression levels in glioma tissues and cells. CCK8, Edu, flow cytometry, wound healing, and transwell assays were used to examined the function of PTBP3 in GBM. qPCR, Immunoblotting, and ubiquitination assays were performed to identify the mechanism of PTBP3. ResultsWe found that PTBP3 was upregulated in GBM, and high expression of PTBP3 correlated with the poor survival of GBM patients. PTBP3 knockdown reduced proliferation, invasion, and migration of GBM. Conversely, overexpressing PTBP3 has an opposite effect. Moreover, PTBP3 had an effect on the EMT of GBM. More importantly, we found that PTBP3 stabilized Twist1 by decreasing its ubiquitination and degradation. Furthermore, orthotopic xenograft models were used to demonstrate the PTBP3 on the development of GBM in vivo. ConclusionThis study proved that PTBP3 promoted tumorigenesis of GBM by stabilizing Twist1, which provided a new therapeutic target for GBM.

Molecular and clinical features of a potential immunotherapy target ELK3 in glioma.

Glioma represents the most prevalent malignant primary brain cancer, and its treatment remains a tremendous challenge. Novel and efficient molecular targets are therefore required for improving diagnosis, survival prediction, and treatment outcomes. Additionally, some studies have shown that immunity is highly associated with glioma progression. Our study aimed to investigate the clinicopathological features, prognostic significance, and immunotherapeutic targetability of ELK3, a member of the erythroblast transformation-specific transcription factor family, in glioma using bioinformatics analyses. ELK3 transcript levels in glioma tissues were evaluated using the Gene Expression Omnibus and The Cancer Genome Atlas databases. Clinical and transcriptomic data of The Cancer Genome Atlas glioma patients were analyzed to identify the molecular and clinical characterizations of ELK3. The prognostic significance of ELK3 was assessed using Cox regression and Kaplan–Meier analysis. The biological pathways related to ELK3 expression were identified by gene set enrichment analysis. The relationships between ELK3 and inflammatory responses, immune cell infiltration, and immune checkpoints were explored using canonical correlation analysis and gene set variation analysis. ELK3 was upregulated in gliomas, and its high expression was correlated with advanced clinicopathologic features and unfavorable prognosis. Gene set enrichment analysis revealed that several immune-related pathways were tightly linked to high ELK3 expression. gene set variation analysis and correlograms demonstrated that ELK3 was robustly associated with inflammatory and immune responses. Correlation analyses indicated that ELK3 was positively associated with infiltrating immune cells and synergistic with several immune checkpoints. ELK3 may serve as a novel marker of poor prognosis and a potential immunotherapeutic target in glioma.

Calponin 3 Acts as a Potential Diagnostic and Prognostic Marker and Promotes Glioma Cell Proliferation, Migration, and Invasion

Calponin 3 (CNN3) is involved in the proliferation and invasion of cervical cancer and osteosarcoma cells. However, the role of CNN3 in glioma tumorigenesis remains to be elucidated. CNN3 mRNA expression in normal brain tissue and gliomas, including glioblastoma multiforme and lower-grade glioma, was analyzed using GEPIA 2 and Oncomine. CNN3 levels in glioma tissues were identified using immunohistochemical data provided by the Human Protein Atlas website. The relationship between CNN3 mRNA expression and clinical characteristics of patients with glioma was analyzed using the Oncomine database and The Cancer Genome Atlas. The diagnostic value of CNN3 expression in glioma was analyzed using receiver operating characteristic analysis according to The Cancer Genome Atlas and Genotype-Tissue Expression data. The relationship between CNN3 and prognosis was analyzed using GEPIA 2. The function of CNN3 knockdown in glioma cell lines was analyzed using cell proliferation, Transwell, and Western blot assays. Both mRNA and protein levels of CNN3 were distinctly higher in lower-grade glioma and glioblastoma multiforme tissues than those in normal brain tissues, particularly glioblastoma. A higher CNN3 mRNA level had significant relationship with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, and 1p/19q noncodeletion. CNN3 mRNA expression is a highly accurate marker for the diagnosis of glioma. Patients with glioma in the high-CNN3 group had significantly lower disease-free survival and survival rates. In addition, CNN3 silencing significantly inhibited cell proliferation, migration, invasion, and the phosphorylation of P65 NF-κB. CNN3 expression is increased in glioma, particularly glioblastoma. Silencing CNN3 expression inhibited the proliferation, migration, and invasion of glioma cell lines.

N-myc Downstream-Regulated Gene 1 (NDRG1) Regulates Vascular Endothelial Growth Factor A (VEGFA) and Malignancies in Glioblastoma Multiforme (GBM).

Background NDRG1 has been reported to exhibit relatively low expression levels in glioma tissues compared with adjacent brain tissues. Additionally, NDRG1 is reported to be a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. However, its exact roles in GBM are still unknown. Methods Gene Expression Profiling Interactive Analysis (GEPIA) was employed to evaluate the expression level of NDRG1 in GBM. After the introduction of NDRG1, proliferation, analyses of colony formation, migration, and invasion capacities were performed. A luciferase reporter assay was performed to detect the effect of NDRG1 on the vascular endothelial growth factor A (VEGFA) promoter. Results In this study, data from GBM and healthy individuals were retrospectively collected by employing GBM, and VEGFA was found to be differentially expressed in GBM tissues compared with adjacent brain tissues. Furthermore, NDRG1 expression is positively correlated with VEGFA expression, but not expression of the other two VEGF isoforms, VEGFB and VEGFC. In the glioma cell lines U87MG and U118, overexpression of NDRG1 significantly upregulated VEGFA. By performing a dual-luciferase reporter assay, it was observed that overexpressed NDRG1 transcriptionally activated VEGFA. Expectedly, overexpression of NDRG1 decreased cell viability by blocking cell cycle phases at G1 phase. Additionally, overexpression of NDRG1 inhibited invasion, colony formation, and tumor formation in soft agar. Remarkably, VEGFA silencing or blockade of VEGF receptor 2 (VEGFR2) further inhibited malignant behaviors in soft agar, including proliferation, invasion, colony formation, and tumor formation. Conclusions NDRG1-induced VEGFA exerts protective effects in GBM via the VEGFA/VEGFR2 pathway. Therefore, targeting both NDRG1 and VEGFA may represent a novel therapy for the treatment of GBM.

GBP2 facilitates the progression of glioma via regulation of KIF22/EGFR signaling

Identifying the mechanism of glioma progression is critical for diagnosis and treatment. Although studies have shown that guanylate-binding protein 2(GBP2) has critical roles in various cancers, its function in glioma is unclear. In this work, we demonstrate that GBP2 has high expression levels in glioma tissues. In glioma cells, depletion of GBP2 impairs proliferation and migration, whereas overexpression of GBP2 enhances proliferation and migration. Regarding the mechanism, we clarify that epidermal growth factor receptor (EGFR) signaling is regulated by GBP2, and also demonstrate that GBP2 interacts directly with kinesin family member 22(KIF22) and regulates glioma progression through KIF22/EGFR signaling in vitro and in vivo. Therefore, our study provides new insight into glioma progression and paves the way for advances in glioma treatment.

Long Non-Coding RNA HCG11 Inhibits Glioma Cells Proliferation and Migration through Decoying miR-590-3p and Up-Regulating CADM2

Background: Long non-coding RNAs are reportedly endowed with the function of promoting or inhibiting cancer occurrence and development. The emphasis of this study was placed on the effect of lncRNA HLA complex group 11 (HCG11) on glioma progression, as well as its mechanism. Methods: Quantitative real-time polymerase chain reaction was utilized for detecting HCG11, miR-590-3p, and CAMD2 mRNA expression levels in glioma tissues. Western blot was adopted to examine cell adhesion molecule (CADM2) protein expression. Cell counting kit-8, BrdU, Transwell and wound healing assays were employed for investigating the malignant biological behaviors of glioma cells. RNA immunoprecipitation assay and dual-luciferase reporter assay were performed to prove the relationship between miR-590-3p and HCG11, as well as CADM2 and miR-590-3p. Results: HCG11 expression was lower in glioma tissues compared with that in paracancerous tissues, and its expression level was negatively correlated with WHO tumor stage. In addition, compared with in astrocyte cell line, the expression of HCG11 was lower in glioma cells. Functional experiments showed that HCG11 inhibited glioma cells migration and proliferation, while miR-590-3p facilitated these processes. Acting as a competitive endogenous RNA, HCG11 adsorbed miR-590-3p and upregulated the expression of CADM2, the target gene of miR-590-3p. Conclusions: HCG11 suppresses glioma cells proliferation and migration through regulating the miR-590-3p/CADM2 molecular axis.

MiR-138-5p Inhibits the Growth and Invasion of Glioma Cells by Regulating WEE1.

Background Accumulating evidence has demonstrated the role of differentially expressed miRNAs in glioma progression. Our previous bioinformatics analyses revealed a role of miR-138-5p in glioma. miR-138-5p was decreased in various tumors, and He et al. found that miR-138-5p had an inhibitory effect on glioma cells in 2021. However, the role of miR-138-5p in the development of glioma and the underlying mechanism is unknown. In this study, we explored whether miR-138-5p affects the biology of glioma by regulating WEE1 expression. Methods miR-138-5p and WEE1 G2 checkpoint kinase (WEE1) RNA and protein expression levels in glioma tissues were detected with qRT-PCR and western blotting, respectively. The effects of miR-138-5p and WEE1 on glioma cell migration and invasion were investigated using Transwell assays. CCK-8 assay was used to measure the effects of miR-138-5p and WEE1 on glioma cell proliferation. The mortality of glioma cells transfected with miR-138-5p and WEE1 was measured with flow cytometry. The relationship between miR-138-5p and WEE1 was explored using a luciferase reporter analysis. Results Functional studies indicated that overexpression of miR-138-5p suppressed cell proliferation, migration, and invasion and promoted death in glioma cell lines. WEE1 was identified as a target of miR-138-5p, and overexpression of miR-138-5p significantly suppressed the levels of WEE1. Moreover, reintroduction of WEE1 partially abrogated miR-138-5p-induced suppression of motility and invasion in glioma cells. Conclusion The low expression of miR-138-5p in glioma suggests a tumor suppressor role for this miRNA. miR-138-5p suppresses glioma progression by regulating WEE1. These data provide new insights into the molecular mechanism of glioma.

Mesenchymal stem cells shuttling miR-503 via extracellular vesicles enhance glioma immune escape

ABSTRACT Glioma is emerging as an aggressive type of glioma characterized by invasive growth pattern and dismal oncologic outcomes. microRNAs (miRNAs) have been attracting research attention in tumorigenesis. Herein, the aim of the current investigation was to explore the functional role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing miR-503 in glioma. The glioma tissues and corresponding normal brain tissues were collected from patients with glioma, followed by quantification of miR-503, kinesin family member 5A (KIF5A) and interleukin-7 (IL-7). EVs were isolated from bone marrow MSCs and identified by transmission electron microscope and nanoparticle tracking analysis. EVs from miR-503 mimic-transfected MSCs, miR-503 agomir,, oe-KIF5A, or sh-IL-7 was delivered into glioma cells to determine their effects on biological behaviors of glioma and T cells as well as the release of immunosuppressive factors. Lastly, a mouse model of glioma was developed to validate the function in vivo. miR-503 was expressed at a high level in glioma tissues while KIF5A was poorly expressed and targeted by miR-503. Furthermore, miR-503 loaded in MSC-EVs or upregulated miR-503 was demonstrated to facilitate glioma cell proliferation, migration and invasion accompanied by promoted release of immunosuppressive factors. Effects of overexpressed KIF5A on T cell behavior modulation were dependent on the IL-7 signaling pathway. Such results were reproduced in mice with glioma. Collectively, the discovery of miR-503 incorporated in MSC-EVs being a regulator that controls immune escape in glioma provides a novel molecular insight that holds promises to develop therapeutic strategies against glioma.

MicroRNA-3148 inhibits glioma by decreasing DCUN1D1 and inhibiting the NF-kB pathway.

Glioma, which originates in the brain, is the most aggressive tumor of the central nervous system. It has been shown that microRNA (miRNA) controls the proliferation, migration and apoptosis of glioma cells. The objective of the present study was to measure microRNA-3148 (miR-3148) expression and investigate its impact on the pathogenetic mechanism of glioma. In the present study, reverse transcription-quantitative real-time PCR was employed to detect miR-3148 expression levels in glioma tissues and cell lines. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and Transwell migration assay were performed to assess the influence of miR-3148 on the malignant biological behavior of glioma cells. The biological functions of miR-3148 in glioma were examined via a xenograft tumor growth assay. Furthermore, the association between miR-3148 and DCUN1D1 was investigated via immunohistochemistry, dual-luciferase reporter assay and western blotting. It was observed that miR-3148 was expressed at low levels in glioma cells, and this represented a poor survival rate. In addition, an increased level of miR-3148 in cells and animal models inhibited glioma cell migration and proliferation. Moreover, miR-3148 decreased DCUN1D1 and curbed the nuclear factor κ enhancer binding protein (NF-κB) signaling pathway, thus decreasing the growth of glioma. Thus, miR-3148 is expressed within glioma tissues at low levels where it suppresses glioma by curbing the NF-κB pathway and lowering DCUN1D1.

LncRNA CDKN2B-AS1 contributes to glioma development by regulating the miR-199a-5p/DDR1 axis.

Although cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is upregulated in glioma, its function and potential mechanism in glioma remain unclear. CDKN2B-AS1 level in glioma tissues and cell lines LN229, U251, and U87 was measured by qRT-PCR. Loss-of-function assays using short hairpin RNA for CDKN2B-AS1 (sh-CDKN2B-AS1) were performed to evaluate the effect of CDKN2B-AS1 on cell invasion, migration, proliferation, and apoptosis. The relationship among CDKN2B-AS1, miR-199a-5p, and DDR1 was determined by bioinformatics analysis and luciferase reporter assay. Rescue experiments were conducted to explore the function of CDKN2B-AS1 and miR-199a-5p in glioma. An in vivo animal model of lentivirally transduced U87 glioma xenografts in mice was established to confirm the role of CDKN2B-AS1. CDKN2B-AS1 is significantly upregulated in glioma tissues and cell lines. CDKN2B-AS1 knockdown significantly inhibits cell proliferation, invasion, and migration, while promoting apoptosis of glioma cell lines U251 and U87. Further, a miR-199a-5p inhibitor attenuates the inhibitory effects of sh-CDKN2B-AS1 on these cell phenotypes. CDKN2B-AS1 positively regulates DDR1 expression by directly sponging miR-199a-5p. Moreover, CDKN2B-AS1 knockdown efficiently inhibits U87 tumor xenograft growth in mice. Our study reveals that CDKN2B-AS1 promotes glioma development by regulating the miR-199a-5p/DDR1 axis, suggesting that this lncRNA might be a potential therapeutic target.

MicroRNA-25 promotes cell proliferation, migration and invasion in glioma by directly targeting cell adhesion molecule 2.

Numerous microRNAs (miRNAs/miRs) have been demonstrated to serve oncogenic or suppressive roles in glioma. Exploration of the underlying molecular mechanism of miRNAs in the development and progression of glioma is beneficial for the identification of novel therapeutic targets. In the present study, the function of miR-25 in glioma progression, as well as its underlying mechanism, were investigated. It was determined that miR-25 was significantly upregulated in glioma tissues and cell lines compared with normal brain tissues and cells, respectively. Furthermore, high expression levels of miR-25 were associated with an advanced clinical stage. The knockdown of miR-25 expression significantly reduced glioma cell proliferation, migration and invasion. Cell adhesion molecule 2 (CADM2) was identified as a direct target of miR-25 in glioma cells. Moreover, CADM2 expression level was significantly downregulated and inversely correlated with miR-25 expression level in glioma tissues, indicating that the expression of CADM2 was negatively regulated by miR-25. The inhibition of CADM2 expression counteracted the effects on glioma cell proliferation, migration and invasion caused by miR-25 downregulation. Furthermore, CADM2 knockdown considerably promoted the proliferation and migration of glioma cells. In summary, the present study demonstrated that miR-25 was significantly upregulated in glioma and that it promoted glioma cell proliferation, migration and invasion, at least partially, by directly targeting CADM2. These findings expanded the understanding of the molecular mechanism that underlies glioma progression.

CircWEE1/miR-138 axis promotes the malignant progression of glioma by regulating SIRT1.

BackgroundThis study aims to reveal the potential impact of circWEE1 on the malignant progression of gliomas and its mechanism.MethodsReal-time quantitative polymerase chain reaction (qRT-PCR) were used to detect circWEE1 levels in glioma tissues and cell lines. The relationship between circWEE1 expression and glioma metastasis was analyzed.ResultsAfter knocking out or over-expressing circWEE1, the effects on glioma cells were examined separately. Subsequently, the regulatory relationship of circWEE1 to miR-138 was detected by a dual luciferase reporter gene. In addition, we evaluated the role of silent information regulator 1 (SIRT1) in the progression of gliomas affected by circWEE1 through a rescue experiment. CircWEE1 was significantly up-regulated in glioma tissues and cell lines. At the same time, its expression level was significantly higher in glioma patients with lymphatic or distant metastasis than in glioma patients with non-metastasis. The down-regulation of circWEE1 reduced the viability, migration, and invasion ability of T98-G cells. The expression of miR-138 is negatively regulated by WEE1, while miR-138 directly targets and regulates the expression of SIRT1.ConclusionsThe rescue experiment confirmed that SIRT1 is a regulator of circWEE1 in the malignant progression of glioma. In summary, the CircWEE1/miR-138 axis may regulate SIRT1 to promote malignant progression in glioma.

Glioma-Derived TSP2 Promotes Excitatory Synapse Formation and Results in Hyperexcitability in the Peritumoral Cortex of Glioma.

Seizures are common in patients with glioma, especially low-grade glioma (LGG). However, the epileptogenic mechanisms are poorly understood. Recent evidence has indicated that abnormal excitatory synaptogenesis plays an important role in epileptogenesis. The thrombospondin (TSP) family is a key regulator of synaptogenesis. Thus, this study aimed to elucidate the role of TSP2 in epileptogenesis in glioma-related epilepsy. The expression of TSP2 was increased in tumor tissue specimens from LGG patients, and this increase may have contributed to an increase in the density of spines and excitatory synapses in the peritumoral area. A glioma cell-implanted rat model was established by stereotactic implantation of wild-type TSP2-expressing, TSP2-overexpressing or TSP2-knockout C6 cells into the neocortex. Similarly, an increase in the density of excitatory synapses was also observed in the peritumoral area of the implanted tumor. In addition, epileptiform discharges occurred in the peritumoral cortex and were positively correlated with the TSP2 level in glioma tissues. Moreover, α2δ1/Rac1 signaling was enhanced in the peritumoral region, and treatment with the α2δ1 antagonist gabapentin inhibited epileptiform discharges in the peritumoral cortex. In conclusion, glioma-derived TSP2 promotes excitatory synapse formation, probably via the α2δ1/Rac1 signaling pathway, resulting in hyperexcitability in the peritumoral cortical networks, which may provide new insight into the epileptogenic mechanisms underlying glioma-related epilepsy.

Up-regulation of MARVEL domain-containing protein 1 (MARVELD1) accelerated the malignant phenotype of glioma cancer cells via mediating JAK/STAT signaling pathway.

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.