Glioma Development Research Articles

Study on in vitro therapeutic impact of 17-ꞵ Estradiol on Glioblastoma cell lines

Glioblastomas (GBM) or grade IV astrocytomas is the most aggressive and frequent tumor in the Central Nervous System (CNS). GBM treatment mainly consists of surgical resection and radio and/or chemotherapy. However, due to its infiltration capacity, it is practically impossible to completely extract the tumor and it relapses. Aberrant EGFR expression is observed in GBM including EGFR mutation, rearrangement and deletions. Blood brain barrier is one of the major obstacles which prevents the entry of larger molecules into the brain. Hence a small molecule, with lesser neurotoxicity should be developed in treating GBM or any other brain related diseases. Previous studies have reported the therapeutic potency of 17-ꞵ Estradiol in treating breast cancer, but little is known about the therapeutic role of estrogen signalling in the development and progression of gliomas. Estradiol being the small molecule has molecular weight of 272.4g/mol. It is a lipophilic molecule and therefore it can pass through the blood brain barrier by passive diffusion and could be considered as a therapeutic molecule in treating GBM. Present study showed that 17-ꞵ Estradiol inhibited the migration, colony formation in GBM cell lines. Further it induced early and late apoptosis and arrested the cell cycle at S-Phase of the cell cycle. EGFR and downstream EGFR associated protein expression were also reduced upon exposure of GBM cell lines to E2. These results show that 17-ꞵ Estradiol could be considered as a therapeutic molecule in GBM treatment.

A prognostic signature based on snoRNA predicts the overall survival of lower-grade glioma patients.

Small nucleolar RNAs (snoRNAs) are a group of non-coding RNAs enriched in the nucleus which direct post-transcriptional modifications of rRNAs, snRNAs and other molecules. Recent studies have suggested that snoRNAs have a significant role in tumor oncogenesis and can be served as prognostic markers for predicting the overall survival of tumor patients. We screened 122 survival-related snoRNAs from public databases and eventually selected 7 snoRNAs that were most relevant to the prognosis of lower-grade glioma (LGG) patients for the establishment of the 7-snoRNA prognostic signature. Further, we combined clinical characteristics related to the prognosis of glioma patients and the 7-snoRNA prognostic signature to construct a nomogram. The prognostic model displayed greater predictive power in both validation set and stratification analysis. Results of enrichment analysis revealed that these snoRNAs mainly participated in the post-transcriptional process such as RNA splicing, metabolism and modifications. In addition, 7-snoRNA prognostic signature were positively correlated with immune scores and expression levels of multiple immune checkpoint molecules, which can be used as potential biomarkers for immunotherapy prediction. From the results of bioinformatics analysis, we inferred that SNORD88C has a major role in the development of glioma, and then performed in vitro experiments to validate it. The results revealed that SNORD88C could promote the proliferation, invasion and migration of glioma cells. We established a 7-snoRNA prognostic signature and nomogram that can be applied to evaluate the survival of LGG patients with good sensitivity and specificity. In addition, SNORD88C could promote the proliferation, migration and invasion of glioma cells and is involved in a variety of biological processes related to DNA and RNA.

CircIQGAP1 regulates RCAN1 and RCAN2 through the mechanism of ceRNA and promotes the growth of malignant glioma

Circular RNA (circRNA) is one of non-coding RNA with specific circular structure, which has been found to be involved in regulating a series of malignant biological behaviors in many malignant tumors. In this study, based on the IDH1 molecular typing of gliomas, we identified a significant downregulation of circRNA (circIQGAP1) expression in IDH1 mutant gliomas by high-throughput sequencing. In 79 tissue samples, we confirmed that circIQGAP1 expression was significantly downregulated in IDH1 mutant gliomas, and that low circIQGAP1 expression was positively associated with better prognosis. Knockdown of circIQGAP1 in glioma cell lines inhibited glioma cell malignancy and conversely overexpression of circIQGAP1 promoted glioma malignancy. circIQGAP1 regulated glioma cell migration, proliferation, invasion and apoptosis through miR-1256/RCAN1/Bax/Bcl-2/Caspase3 and miR-622/RCAN2/Bax/Bcl-2/Caspase3 axes. These results suggest that circIQGAP1 plays an important role in glioma development, promotes tumor growth, and is a potential therapeutic target for glioma.

SENP1-mediated SUMOylation of SIRT1 affects glioma development through the NF-κB pathway

Gliomas are the most common primary brain tumors in adults. Although they exist in different malignant stages, most gliomas are clinically challenging because of their infiltrative growth patterns and inherent relapse tendency with increased malignancy. Epigenetic alterations have been suggested to be an important factor for glioma genesis. Using mRNA probe hybridization, we identified SUMO-specific protease 1 (SENP1) as the most significantly upregulated SUMOylation regulator in glioma. Moreover, SENP1 was overexpressed in gliomas and predicted poor prognoses. Depletion of SENP1 reduced glioma cell activity, cycle arrest, and increased apoptotic activity. Mechanistically, SENP1 inhibited the protein expression of sirtuin 1 (SIRT1) through de-SUMOylation, and SIRT1 inhibited the activity of nuclear factor kappaB (NF-κB) by deacetylation. Rescue experiments revealed that downregulation of SIRT1 reversed the inhibitory effect of sh-SENP1 on glioma cell malignant phenotype, while downregulation of NF-κB reversed the activating effect of sh-SIRT1 on glioma cell malignant phenotype. Thus, SENP1-mediated de-SUMOylation of SIRT1 might be therapeutically important in gliomas.

The HNF4A-CHPF pathway promotes proliferation and invasion through interactions with MAD1L1 in glioma.

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferases that participates in the biosynthesis of chondroitin sulfate (CS). Our previous study showed that silencing CHPF expression inhibited glioma cell proliferation in vitro, but the molecular mechanisms by which CHPF contributes to development of glioma have not been characterized. In this study, we found that CHPF was up-regulated in glioma tissues and was positively correlated with malignant clinical pathological characteristics of patients with glioma. Silencing CHPF expression inhibited proliferation, colony formation, migration, and cell cycle of glioma cells. Moreover, silencing CHPF suppressed glioma malignance in vivo. Immunoprecipitation, co-immunoprecipitation, GST pulldown, and liquid chromatography-mass spectrometry (LC-MS/MS) assays were used to verify the interaction between CHPF and Mitotic arrest deficient 1-like 1 (MAD1L1). In addition, Chromatin Immunoprecipitation (ChIP)-PCR analysis showed that HNF4A bound to the CHPF promoter region, which indicated that the transcription factor hepatocyte nuclear factor 4A (HNF4A) could regulate the expression of CHPF in glioma cells.

Role of the Microenvironment in Glioma Pathogenesis.

Gliomas are a diverse group of primary central nervous system tumors that affect both children and adults. Recent studies have revealed a dynamic cross talk that occurs between glioma cells and components of their microenvironment, including neurons, astrocytes, immune cells, and the extracellular matrix. This cross talk regulates fundamental aspects of glioma development and growth. In this review, we discuss recent discoveries about the impact of these interactions on gliomas and highlight how tumor cells actively remodel their microenvironment to promote disease. These studies provide a better understanding of the interactions in the microenvironment that are important in gliomas, offer insight into the cross talk that occurs, and identify potential therapeutic vulnerabilities that can be utilized to improve clinical outcomes.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. 129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

High LYRM4-AS1 predicts poor prognosis in patients with glioma and correlates with immune infiltration.

Many researches proved that non-coding RNAs are important in glioma development. We screened the differentially expressed genes through The Cancer Genome Atlas (TCGA) database and identified the molecule LYRM4-AS1 associated with prognosis. As a lncRNA, the expression level and role of LYRM4-AS1 in glioma are inconclusive. Therefore, we attempted to assess the clinical significance, expression and related mechanisms of LYRM4-AS1 in glioma by employing cell experiments and an integrative in silico methodology. RNA-seq data were obtained from UCSC XENA and TCGA datasets. The Gene Expression Omnibus (GEO) database was used to download glioma-related expression profile data. The LYRM4-AS1 expression level was evaluated. Survival curves were constructed by the Kaplan-Meier method. Cox regression analysis was used to analyze independent variables. Patients were divided into high and low expression group base on the median LYRM4-AS1 expression value in glioma tissues. The DESeq2 R package was used to identify differentially expressed genes (DEGs) between two different expression LYRM4-AS1 groups. Gene set enrichment analysis (GSEA) was conducted. Next, the single-sample Gene Set Enrichment Analysis (ssGSEA) was done to quantify the immune infiltration of immune cells in glioma tissues. Gene expression profiles for glioma tumor tissues were used to quantify the relative enrichment score for each immune cell. Spearman correlation analysis was used to analyze the correlation between LYRM4-AS1 and biomarkers of immune cells as well as immune checkpoints in glioma. Finally, assays for cell apoptosis, cell viability and wound healing were conducted to evaluate the function on U87 MG and U251 cells after knocking down LYRM4-AS1. We found that LYRM4-AS1 was upregulated and related to the grade and malignancy of glioma. Survival analyses showed that high expression LYRM4-AS1 patients had poor clinical outcomes (P < 0.01). Cox regression analyses demonstrated that LYRM4-AS1 was an independent risk factor for overall survival (OS) in glioma (HR: 274 1.836; CI [1.278-2.639]; P = 0.001). Enrichment and immune infiltration analysis showed interferon signaling and cytokine-cytokine receptor interaction enriched in the LYRM4-AS1 high-expression phenotype, and LYRM4-AS1 showed significantly positively related to immune infiltration as well as immune checkpoints (P < 0.01). The knockdown of LYRM4-AS1 in U87 MG and U251 cells can inhibit migration and proliferation of cells (P < 0.05). These findings indicated that the increased LYRM4-AS1 may be useful for the diagnosis and prognosis of glioma and might participate in the immune infiltration.

An adult Drosophila glioma model to highlight metabolic dysfunctions and evaluate the role of the serotonin 5-HT7 receptor as a potential therapeutic target.

Gliomas account for 50% of brain cancers and are therefore the most common brain tumors. Molecular alterations involved in adult gliomas have been identified and mainly affect tyrosine kinase receptors with amplification and/or mutation of the epidermal growth factor receptor (EGFR) and its associated signaling pathways. Several targeted therapies have been developed, but current treatments remain ineffective for glioblastomas, the most severe forms. Thus, it is a priority to identify new pharmacological targets. Drosophila glioma models established in larvae and adults are useful to identify new genes and signaling pathways involved in glioma progression. Here, we used a Drosophila glioma model in adults, to characterize metabolic disturbances associated with glioma and assess the consequences of 5-HT7 R expression on glioma development. First, by using in vivo magnetic resonance imaging, we have shown that expression of the constitutively active forms of EGFR and PI3K in adult glial cells induces brain enlargement. Then, we explored altered cellular metabolism by using high-resolution magic angle spinning NMR and 1 H-13 C heteronuclear single quantum coherence solution states. Discriminant metabolites identified highlight the rewiring of metabolic pathways in glioma and associated cachexia phenotypes. Finally, the expression of 5-HT7 R in this adult model attenuates phenotypes associated with glioma development. Collectively, this whole-animal approach in Drosophila allowed us to provide several rapid and robust phenotype readouts, such as enlarged brain volume and glioma-associated cachexia, as well as to determine the metabolic pathways involved in glioma genesis and finally to confirm the interest of the 5-HT7 R in the treatment of glioma.

The association between NRF2 transcriptional gene dysregulation and IDH mutation in Grade 4 astrocytoma

Abstract Objectives Nuclear factor erythroid-2-related factor 2 (NRF2), a transcriptional gene factor related to nuclear factor erythroid 2, plays a role in the development of gliomas with isocitrate dehydrogenase (IDH) mutation. Its impact on tumour recurrence has seldom been investigated. Methods A group of 34 patients diagnosed with Grade 4 astrocytoma was included in a retrospective cohort. NRF2 protein and gene expressions were assessed using different profiling assays. The association between IDH mutation, NRF2 expression, and tumor recurrence was investigated. Results The mean patients’ age in this study was 50 years. Out of the total number of tumors analyzed, 21 of them had IDH mutation. NRF2 protein expression was found to be overexpressed in 27 tumors and reduced in 7 tumors. Additionally, NRF2 gene was upregulated in 24 tumors and downregulated in 10 tumors. Insignificant statistical difference was observed in recurrence-free interval (RFI) between patients with upregulated or downregulated NRF2 gene or protein expressions (p-value&gt;0.05). However, this relationship is distinctive when NRF2 expression was compared to IDH mutation. Tumors with different levels of NRF2 expressions and IDH mutations showed significant statistical variation in RFI (p-value=0.001). There was insignificant impact on RFI among patients receiving different chemotherapies (TMZ or TMZ plus) who had abnormal NRF2 gene activities (p-value=0.97). Conclusions WHO-Grade 4 astrocytoma with IDH mutation and altered NRF2 expression showed a delayed tumor recurrence compared to IDH-wildtype glioblastoma.

CircSOBP suppresses the progression of glioma by disrupting glycolysis and promoting the MDA5-mediated immune response

Glioma, an aggressively growing and highly malignant brain tumor, poses substantial therapeutic challenges due to its resistance to radiotherapy and chemotherapy. Recent research has identified circRNAs as pivotal players in glioma formation and development. However, the roles of circRNA in the metabolic and immune regulation of glioma are unclear. In this study, circSOBP expression was significantly downregulated in glioma cells and specimens. Functionally, enhanced circSOBP expression mitigated cell proliferation, invasion, migration, and glycolysis in gliomas. Mechanistically, circSOBP inhibited glycolysis and activated the MDA5-mediated IKKε/TBK1/IRF3 signaling pathway by binding TKFC proteins. Furthermore, the elevated levels of IFN-I induced by the MDA5 pathway increased the number and activity of CD8+ T and NK cells in the immune response of the animal models. In summary, our findings have emphasized the critical role of circSOBP in binding and modulating TKFC protein, offering potential therapeutic avenue for targeting glioma metabolism and immunological reprogramming.

Arylsulfatase D is a prognostic biomarker that promotes glioma cells progression through JAK2/STAT3 pathway and M2 macrophage infiltration.

Arylsulfatase D (ARSD) belongs to the sulfatase family and plays a crucial role in maintaining the proper structure of bone and cartilage matrix. Although several researches have revealed the functions of ARSD in tumor progression, the prognostic value of ARSD in glioma and the related mechanisms have not been fully investigated. We performed a pan-cancer analysis of ARSD, and investigated the relationship between expression of ARSD and overall survival (OS) in multiple glioma datasets. ROC curves and nomograms were created to investigate the predictive capacity of ARSD. Immune and analysis were conducted to investigate the mechanisms underlying the roles of ARSD in glioma. Glioma tissue samples were collected to verify the expression of ARSD in glioma, while the functions of ARSD were explored using cell experiment. M2 macrophage infiltration assay was used to determine the relation between ARSD and tumor immune microenvironment. Survival analysis indicated that individuals with high ARSD expression in glioma had a shorter survival time. Cox analysis showed that ARSD had a good ability for predicting prognosis in glioma. Immune analysis suggested that ARSD could regulate immune cell infiltration and affect the Cancer-Immunity Cycle to create an immunosuppressive environment. Combined with cell experiment and bioinformatic analysis, we found that ARSD can promote glioma progression through regulation of JAK2/STAT3 pathway and M2 macrophage infiltration. Our study found that ARSD can promote glioma development by regulating immune microenvironment and JAK2/STAT3 signaling pathway, which provided a potential therapy target for glioma treatment.

Integrative analysis of multi-omics data reveals a pseudouridine-related lncRNA signature for prediction of glioma prognosis and chemoradiotherapy sensitivity

BackgroundGlioblastoma is the most common type of glioma with a high incidence and poor prognosis, and effective medical treatment remains challenging. Pseudouridine (Ψ) is the first post-transcriptional modification discovered and one of the most abundant modifications to RNA. However, the prognostic value of Ψ-related lncRNAs (ΨrLs) for glioma patients has never been systematically evaluated. This study aims to construct a risk model based on ΨrLs signature and to validate the predictive efficiency of the model. MethodTranscriptomic data, genomic data, and relevant clinical data of glioma patients were extracted from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). ΨrLs with significant correlation with Ψ-related genes were identified, and univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were used to further select biomarkers and construct a ΨrLs signature risk model. Then, the expression of lncRNAs of ΨrLs signature in multiple glioma cell lines was detected by qPCR. Further, ROC analysis, stratification analysis, correlation analysis, survival analysis, nomogram, enrichment analysis, immune infiltration analysis, chemoradiotherapy sensitivity analysis, somatic mutation, and recurrent copy number variation (CNV) analysis were used to validate the predictive efficiency of ΨrLs signature in TCGA and CGGA datasets. ResultsA four-lncRNA ΨrLs signature (DNAJC27-AS1, GDNF-AS1, ZBTB20-AS4, and DNMBP-AS1) risk model was constructed. By ROC analysis, stratified analysis, correlation analysis, survival analysis, and nomogram, the signature showed satisfactory predictive efficiency. Functional enrichment analysis revealed the differences in immune-related biological processes between high- and low-risk groups. Immune infiltration analysis showed that the high-risk group had lower tumor purity and higher stromal, immune and ESTIMATE scores. Mitoxantrone was identified as effective drug for low-risk group of glioma patients. Key genes in glioma development, including IDH1, EGFR, PTEN, etc., were differentially mutated between risk groups. The main recurrent CNVs in low-risk groups were 19q13.42 deletion and 7q34 amplification; 10q23.31 deletion and 12q14.1 in the high-risk group. ConclusionsOur study identified a four-lncRNA ΨrLs signature that effectively predicts the prognosis of glioma patients and may serve as a diagnostic tool. Risk scores of glioma patients generated by the signature is associated with immune-related biological processes and chemoradiotherapy sensitivity. These findings may inform the development of more targeted and effective therapies for glioma patients.

Prognostic biomarker SYK and its correlation with immune infiltrates in glioma.

The tumor microenvironment (TME) provides excellent conditions for the development of glioma. The present study sought to identify the prognostic factors of glioma that could be used to improve the prognosis of patients with this disease. In the present study, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data calculations were employed to estimate the ratio of tumor-infiltrating immune cells and the quantity of immune and stromal components in 698 glioma cases from the Cancer Genome Atlas database. In addition, certain differentially expressed genes were studied by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and single genes associated with prognosis were identified by protein-protein interaction (PPI) network and Cox combined analysis. The immune and stromal scores of the TME were significantly associated with glioma patient survival. By using the PPI network and Cox regression analyses, spleen tyrosine kinase (SYK) was eventually identified as the best prognostic factor for patients with glioma. In addition, Gene Set Enrichment Analysis and CIBERSORT analyses were employed. The former indicated that the high-expression SYK group genes were mainly enriched in immune-related activities. The latter revealed that SYK expression was positively associated with T cell cluster of differentiation 4 memory resting and monocytes. The aforementioned experimental analyses provided the theoretical basis for the biological prediction of SYK. The data indicated that SYK contributed to immune predictors in patients with glioma by facilitating the shift of the TME from immune dominance to metabolic activity. Finally, reverse transcription-quantitative PCR and western blotting were used to verify the single gene expression in glioma cells. This may provide prognostic value for the treatment of glioma.

S100A6 is a potential diagnostic and prognostic biomarker for human glioma.

S100 calcium-binding protein A6 (S100A6) is a protein that belongs to the S100 family. The present study aimed to investigate the function of S100A6 in the diagnosis and survival prediction of glioma and elucidated the potential processes affecting glioma development. The Cancer Genome Atlas database was searched to identify the relationship among S100A6 expression, immune cell infiltration, clinicopathological parameters and glioma prognosis. Several clinical cases were used to verify these findings. S100A6 gene expression was high in glioma tissues, suggesting its diagnostic significance. In particular, S100A6 upregulation in glioma tissues exhibited a significant and positive correlation with the World Health Organization (WHO) grade, histological type, age, sex, primary treatment outcomes, 1p/19q codeletion, isocitrate dehydrogenase (IDH) status, overall survival (OS), progression-free interval and disease-specific survival. Kaplan-Meier and Cox regression analyses revealed that S100A6 gene expression can independently function as a risk factor affecting the prognosis of patients with glioma. Furthermore, Gene Ontology functional enrichment analysis revealed that S100A6 is implicated in immune responses and that the expression profiles of S100A6 are linked to the immune microenvironment. Furthermore, immunohistochemistry revealed that increased S100A6 protein levels are correlated with age, 1p/19q codeletion, IDH status, WHO grade and OS. The present findings suggest that increased S100A6 expression is an indicator of the dismal prognosis of patients with glioma and that it can be used as a potential diagnostic biomarker for this condition.

Impact of propofol versus sevoflurane anesthesia on molecular subtypes and immune checkpoints of glioma during surgery.

Sevoflurane and propofol are two popular anesthetics used during glioblastoma (GBM) surgery. This investigation compared the molecular subtypes and immune checkpoints of cancer cells following GBMsurgery under sevoflurane and propofol anesthesia. The expression profile data and clinical information of glioma samples of different grades were downloaded from The Cancer Genome Atlasdatabase. Weighted gene coexpression network analysiswas used to identify hub modules and key genes related to glioma grades (G2 and G3). The GEO database (GSE179004) was used to retrieve glioma surgical specimens with different anesthetic gene expression profiles. The differential expression of immune checkpoint genes under various anesthetic settings was examined using the R-ggplot2. Compared to sevoflurane, propofol significantly downregulated SERPINI1 and CAMK2A expression. These are also important factors in glioma grading. Simultaneously, SERPINI1 and CAMK2A were also significantly related to the prognosis of GBM and lower-grade gliomapatients and acted as potential tumor suppressors. In addition, propofol increases the expression of the immune checkpoint molecule, PD-L1. Our study revealed that sevoflurane can more effectively prevent the development of glioma after surgery than propofol, and SERPINI1 can be used as a new independent prognostic factor for glioma.

Altered plasma metabolite levels can be detected years before a glioma diagnosis.

Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. Since gliomas are currently detected late, a liquid biopsy for early detection could affect the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 prediagnostic glioma cases and 550 healthy controls from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We identified 93 significantly altered metabolites related to glioma development up to 8 years before diagnosis. Out of these metabolites, a panel of 20 selected metabolites showed strong disease correlation and a consistent progression pattern toward diagnosis in both the NSHDS and EPIC cohorts, and they separated future cases from controls independently of biological sex. The blood metabolite panel also successfully separated both lower-grade glioma and glioblastoma cases from controls, up to 8 years before diagnosis in patients within the NSHDS cohort and up to 2 years before diagnosis in EPIC. Pathway enrichment analysis detected metabolites related to the TCA cycle, Warburg effect, gluconeogenesis, and cysteine, pyruvate, and tyrosine metabolism as the most affected.

Ultrafast Detection of Monoamine Oxidase A in Live Cells and Clinical Glioma Tissues Using an Affinity Binding‐Based Two‐Photon Fluorogenic Probe

AbstractAbnormal expression of monoamine oxidase A (MAO−A) has been implicated in the development of human glioma, making MAO−A a promising target for therapy. Therefore, a rapid determination of MAO−A is critical for diagnosis. Through in silico screening of two‐photon fluorophores, we discovered that a derivative of N,N‐dimethyl‐naphthalenamine (pre‐mito) can effectively fit into the entrance of the MAO−A cavity. Substitutions on the N‐pyridine not only further explore the MAO−A cavity, but also enable mitochondrial targeting ability. The aminopropyl substituted molecule, CD1, showed the fastest MAO−A detection (within 20 s), high MAO−A affinity and selectivity. It was also used for in situ imaging of MAO−A in living cells, enabling a comparison of the MAO−A content in human glioma and paracancerous tissues. Our results demonstrate that optimizing the affinity binding‐based fluorogenic probes significantly improves their detection rate, providing a general approach for rapid detection probe design and optimization.

Ultrafast Detection of Monoamine Oxidase A in Live Cells and Clinical Glioma Tissues Using an Affinity Binding-Based Two-Photon Fluorogenic Probe.

Abnormal expression of monoamine oxidase A (MAO-A) has been implicated in the development of human glioma, making MAO-A a promising target for therapy. Therefore, a rapid determination of MAO-A is critical for diagnosis. Through in-silico screening of two-photon fluorophores, we discovered that a derivative of N,N-dimethyl-naphthalenamine (pre-mito) can effectively fit into the entrance of MAO-A cavity. Substitutions on the N-pyridine not only further explore the MAO-A cavity, but also enable mitochondrial targeting ability. The aminopropyl substituted molecule, CD1, showed the fastest MAO-A detection (within 20 s), high MAO-A affinity and selectivity. It was also used for in situ imaging of MAO-A in living cells, enabling a comparison of the MAO-A content in human glioma and paracancerous tissues. Our results demonstrate that optimizing the affinity binding-based fluorogenic probes significantly improves their detection rate, providing a general approach for rapid detection probe design and optimization.

Long Non-coding RNA Prader Willi/Angelman Region RNA 6 Suppresses Glioma Development by Modulating MicroRNA-106a-5p.

As one of the most frequent intracranial tumors, glioma showed invasive development and poor prognosis. lncRNAs have been illustrated to serve as biomarkers in various cancers. Whether the long non-coding RNA Prader Willi/Angelman region RNA 6 (PWAR6) was involved in glioma development and the underlying mechanism was investigated. PWAR6 in glioma was evaluated by polymerase chain reaction and its clinical significance was assessed with a series of statistical analyses. The biological function of PWAR6 was investigated with the cell counting kit 8 and Transwell assay. The potential underlying mechanism was studied with the luciferase reporter assay. The significant downregulation of PWAR6 was observed in glioma, which showed a close relationship with the major clinicopathological features and poor prognosis of patients. PWAR6 restrained cell growth, migration and invasion of glioma, which was alleviated by the overexpression of microRNA-106a-5p (miR-106a-5p). PWAR6 functioned as a prognostic biomarker and tumor suppressor of glioma through regulating miR-106a-5p.