Progression Of Glioma Cells Research Articles

RAB32 promotes glioma cell progression by activating the JAK/STAT3 signaling pathway.

This study aimed to investigate the role of RAB32 in glioblastomas and its molecular mechanisms that regulate gliomas. The expression and prognostic value of RAB32 were evaluated using western blotting and the Gene Expression Profiling Interactive, Chinese Glioma Genome Atlas, and The Cancer Genome Atlas databases. Lentivirus containing sh-RAB32 or OE-RAB32 was used to manipulate RAB32 expression in glioma cells. The effects of RAB32 on cell proliferation, migration, and invasion were determined by western blotting, cell counting kit-8, plate cloning, wound healing, and transwell assays. Gene set enrichment analysis was used to screen for associations between the JAK/STAT3 signaling pathway and RAB32. The role of this pathway was verified using JAK/STAT3 inhibitors. RAB32 expression was significantly upregulated in patients with glioma and in glioma cell lines. The expression level was positively correlated with the glioma grade and served as an independent prognostic factor. In vitro experiments revealed that RAB32 knockdown inhibited glioblastoma cell proliferation, migration, and invasion, while the opposite effects were observed with overexpression and could be inhibited by the JAK/STAT3 inhibitor BP-1-102. RAB32 promotes malignant progression of glioblastoma cells through the JAK/STAT signaling pathway, providing new possibilities for therapeutic targets for glioblastoma.

RETRACTION: MiR-129-5p Inhibits Glioma Cell Progression InVitro and InVivo by Targeting TGIF2.

Y. Diao, B. Jin, L. Huang, and W. Zhou, "MiR-129-5p Inhibits Glioma Cell Progression InVitro and InVivo by Targeting TGIF2," Journal of Cellular and Molecular Medicine 22, no. 4 (2018): 2357-2367. doi: 10.1111/jcmm.13529. The above article, published online on 12 February 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan Constantinescu; The Foundation for Cellular and Molecular Medicine; and John Wiley and Sons Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed inappropriate duplications of image panels (Figure4A and 6G) between this and other articles that were either previously published or published later in the same year by different group of authors. Thus, the editors consider the conclusions of this manuscript substantially compromised. The authors and their institute were informed of the concerns and the decision to retract but they remained unresponsive.

488P ITGA2 promotes glioma cell stemness and progression by activating the AKT pathway

488P ITGA2 promotes glioma cell stemness and progression by activating the AKT pathway

Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration.

Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.

The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway

IntroductionGlioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated. ObjectivesThis research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma. MethodsThe amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules. ResultsThe upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4. ConclusionOur findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.

CircNUP98 promotes the malignant behavior of glioma cells through the miR-520f-3p/ELK4 axis.

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si-NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)-520f-3p, as well as between miR-520f-3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR-520f-3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR-520f-3p, thereby relieving the inhibitory effect of miR-520f-3p on ELK4. Moreover, inhibition of miR-520f-3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR-520f-3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Identification and validation of a glycolysis-related taxonomy for improving outcomes in glioma.

Reprogramming of glucose metabolism is a prominent abnormal energy metabolism in glioma. However, the efficacy of treatments targeting glycolysis varies among patients. The present study aimed to classify distinct glycolysis subtypes (GS) of glioma, which may help to improve the therapy response. The expression profiles of glioma were downloaded from public datasets to perform an enhanced clustering analysis to determine the GS. A total of 101 combinations based on 10 machine learning algorithms were performed to screen out the most valuable glycolysis-related glioma signature (GGS). Through RSF and plsRcox algorithms, adrenomedullin (ADM) was eventually obtained as the most significant glycolysis-related gene for prognostic prediction in glioma. Furthermore, drug sensitivity analysis, molecular docking, and invitro experiments were utilized to verify the efficacy of ADM and ingenol mebutate (IM). Glioma patients were classified into five distinct GS (GS1-GS5), characterized by varying glycolytic metabolism levels, molecular expression, immune cell infiltration, immunogenic modulators, and clinical features. Anti-CTLA4 and anti-PD-L1 antibodies significantly improved the prognosis for GS2 and GS5, respectively. ADM has been identified as a potential biomarker for targeted glycolytic therapy in glioma patients. Invitro experiments demonstrated that IM inhibited glioma cell progression by inhibiting ADM. This study elucidates that evaluating GS is essential for comprehending the heterogeneity of glioma, which is pivotal for predicting immune cell infiltration (ICI) characterization, prognosis, and personalized immunotherapy regimens. We also explored the glycolysis-related genes ADM and IM to develop a theoretical framework for anti-tumor strategies targeting glycolysis.

The CircHAS2/RPL23/MMP9 Axis Facilitates Brain Tumor Metastasis

Abstract Background: Circular RNAs (circRNAs) regulate tumor development by interacting with microRNAs. However, limited research has been conducted on the roles of circRNAs in gliomas. Therefore, we sought to demonstrate the function and molecular mechanism of circHAS2 in gliomas. Methods: CircHAS2, hsa-miR-508-3p, RPL23, and MMP9 mRNA levels were assessed with qRT-PCR. RPL23 and MMP9 protein levels were determined with western blotting and immunohistochemical staining. Glioma cell migration and invasion were assessed with Transwell assays. The interaction between hsa-miR-508-3p and circHAS2 or RPL23 was predicted with RNAhybrid and miRanda, and confirmed through luciferase reporter assays. The effects of circHAS2 on glioma cells were demonstrated in a nude mouse orthotopic xenograft glioma model. Results: We computationally analyzed the differentially expressed circRNAs in glioma tissues by using the GEO database. The screening indicated that circHAS2 was located primarily in the cytoplasm. Functionally, silencing of circHAS2 inhibited glioma migration and invasion. Mechanically, hsa-miR-508-3p was identified as a downstream target of circHAS2. CircHAS2 was found to regulate RPL23 and influence MMP9 via hsa-miR-508-3p, thereby promoting glioma migration and invasion. Moreover, inhibition of circHAS2 impeded the progression of U87 glioma cells in vivo. Conclusion: CircHAS2 regulates RPL23 and subsequent MMP9 expression by sponging hsa-miR508-3p in glioma cells.

Turkish coffee suppresses the progression of C6 glioma cells via the activation of apoptosis

Turkish coffee suppresses the progression of C6 glioma cells via the activation of apoptosis

METTL3-mediated HOTAIRM1 promotes vasculogenic mimicry icontributionsn glioma via regulating IGFBP2 expression

BackgroundHOTAIRM1 is revealed to facilitate the malignant progression of glioma. Vasculogenic mimicry (VM) is critically involved in glioma progression. Nevertheless, the molecular mechanism of HOTAIRM1 in regulating glioma VM formation remains elusive. Thus, we attempted to clarify the role and mechanism of HOTAIRM1 in VM formation in glioma.MethodsqRT-PCR and western blot assays were used to evaluate the gene and protein expression levels of HOTAIRM1 in glioma patient tissue samples and cell lines. The role of HOTAIRM1 in glioma cell progression and VM formation was explored using a series of function gain-and-loss experiments. RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and mechanism experiments were conducted to assess the interaction between HOTAIRM1/METTL3/IGFBP2 axis. Furthermore, rescue assays were conducted to explore the regulatory function of HOTAIRM1/METTL3/IGFBP2 in glioma cell cellular processes and VM formation.ResultsWe found that HOTAIRM1 presented up-regulation in glioma tissues and cells and overexpression of HOTAIRM1 facilitated glioma cell proliferation, migration, invasion, and VM formation. Furthermore, overexpression of HOTAIRM1 promoted glioma tumor growth and VM formation capacity in tumor xenograft mouse model. Moreover, HOTAIRM1 was demonstrated to interact with IGFBP2 and positively regulated IGFBP2 expression. IGFBP2 was found to promote glioma cell malignancy and VM formation. Mechanistically, METTL3 was highly expressed in glioma tissues and cells and was bound with HOTAIRM1 which stabilized HOTAIRM1 expression. Rescue assays demonstrated that METTL3 silencing counteracted the impact of HOTAIRM1 on glioma cell malignancy and VM formation capacity.ConclusionHOTAIRM1, post-transcriptionally stabilized by METTL3, promotes VM formation in glioma via up-regulating IGFBP2 expression, which provides a new direction for glioma therapy.Graphical

CNSC-19. HYPOXIA-INDUCED NEURONAL ACTIVITY IN GLIOMA PATIENTS POLARIZES MICROGLIA BY POTENTIATING RNA M6A DEMETHYLATION

Abstract Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. In this study, by applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. Here, we demonstrate that hypoxia induces glioma stem cells (GSCs) to produce glutamate, which activates local neurons. The hypoxia-induced neuronal activity promotes GBM progression by facilitating microglial M2 polarization. We found that when microglia were co-cultured with activated neurons, the level of RNA m6A methylation in microglia was impaired, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted regional microglial M2 polarization while cortical neuronal inhibition decreased regional microglial M2 polarization in GBM xenografts. Together, these findings indicate that hypoxic GSC-induced neuronal activation promotes GBM progression by polarizing microglia via decreasing their m6A methylation levels.

Hypoxia-Induced Neuronal Activity in Glioma Patients Polarizes Microglia by Potentiating RNA m6A Demethylation.

Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. By applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. We demonstrate that hypoxia drove glioma stem cells (GSC) to produce higher levels of glutamate, which activated local neurons. Neuronal activity promoted GBM progression by facilitating microglial M2 polarization through enriching miR-200c-3p in neuron-derived exosomes, which decreased the expression of the m6A writer zinc finger CCCH-type containing 13 (ZC3H13) in microglia, impairing methylation of dual specificity phosphatase 9 (DUSP9) mRNA. Downregulation of DUSP9 promoted ERK pathway activation, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted microglial M2 polarization whereas cortical neuronal inhibition decreased microglial M2 polarization in GBM xenografts. miR-200c-3p knockdown in cortical neurons impaired microglial M2 polarization and GBM xenograft growth, even when cortical neurons were activated. Treatment with the anti-seizure medication levetiracetam impaired neuronal activation and subsequently reduced neuron-mediated microglial M2 polarization. These findings indicated that hypoxic GSC-induced neuron activation promotes GBM progression by polarizing microglia via the exosomal miR-200c-3p/ZC3H13/DUSP9/p-ERK pathway. Levetiracetam, an antiepileptic drug, blocks the abnormal activation of neurons in GBM and impairs activity-dependent GBM progression. See related commentary by Cui et al., p. 1073.

DNA methylation-regulated LINC02587 inhibits ferroptosis and promotes the progression of glioma cells through the CoQ-FSP1 pathway

BackgroundLong noncoding RNAs (lncRNAs) are considered key players in the formation and development of tumors. Herein, Gene Expression Profiling Interactive Analysis (GEPIA) was employed as a bioinformatics technology. LINC02587 is differentially expressed in bladder urothelial cancer, glioblastoma, lung adenocarcinoma, lung SCC, melanoma, and other tumor tissue and cells. However, its impact on the emergence of glioma and its mechanism is remaining elusive.MethodsSome of the in vitro assays employed in this study were the CCK-8 / Annexin-V / Transwell assays, colony formation, and wound healing, together with Western blot (WB) evaluation. MSP / BSP assays were employed for assessing the CpG island’s methylation status in the LINC02587 promoter. Through transcriptome, ferroptosis-related experiments, and WB evaluation, it was confirmed that LINC02587 is correlated with the regulation of ferroptosis in tumor cells, and CoQ-Fsp1 is one of its regulatory pathways. Moreover, the underlined in-vitro results were further validated by in-vivo studies.ResultsThe current study shows that the promoter sequence of LINC02587 is regulated by methylation. The silencing of LINC02587 can inhibit cellular proliferative, migrative, and invasive properties, and induce ferroptosis within gliomas through the CoQ-FSP1 pathway.ConclusionsLINC02587 is likely to be a novel drug target in treating glioma.

DNMT1-mediated regulating on FBXO32 promotes the progression of glioma cells through the regulation of SKP1 activity.

Glioma, a prevalent and serious form of brain cancer, is associated with dysregulation of DNA methylation, where DNA methyltransferase-1 (DNMT1) plays a significant role in glioma progression. However, the involvement of F-box protein 32 (FBXO32) in glioma and its regulation by DNMT1-mediated methylation remain poorly understood. In this study, we investigated FBXO32 expression in glioma cells with high DNMT1 expression using the online dataset and correlated it with patient survival. Then impact of elevated FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with the examination of EMT-related proteins. Furthermore, a xenograft model established by injecting glioma cells stably transfected with FBXO32 was used to evaluate tumor growth, volume, and weight. The ChIP assay was employed to study the interaction between DNMT1 and the FBXO32 promoter, revealing that DNMT1 negatively correlated with FBXO32 expression in glioma cells and promoted FBXO32 promoter methylation. Moreover, we investigated the interaction between FBXO32 and SKP1 using Co-IP and GST pulldown assays, discovering that FBXO32 acts as an E3 ubiquitin ligase and promotes SKP1 ubiquitination, leading to its degradation. Interestingly, our findings demonstrated that high FBXO32 expression was associated with improved overall survival in glioma patients. Knockdown of DNMT1 in glioma cells increased FBXO32 expression and suppressed malignant phenotypes, suggesting that FBXO32 functions as a tumor suppressor in glioma. In conclusion, this study reveals a novel regulatory mechanism involving DNMT1-mediated FBXO32 expression in glioma cells, where FBXO32 acts as an E3 ubiquitin ligase to degrade SKP1 via ubiquitination. This FBXO32-mediated regulation of SKP1 activity contributes to the progression of glioma cells. These findings provide important insights into the molecular mechanisms underlying glioma progression and may hold promise for the development of targeted therapies for glioma patients.

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.

SDPS-17 COMPREHENSIVE ANALYSIS OF CELL DIVISION CYCLE ASSOCIATED GENE FAMILY EXPRESSION PATTERN AND PROGNOSIS VALUE REVEALS CDCA2 AS A NOVEL ONCOGENE FOR GLIOMA

Abstract Glioma is the most common central nervous system tumors. Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. The cell division cycle associated proteins (CDCA) family gene is involved in a wide range of biological functions in human cancers. Nevertheless, the expression characteristics of CDCAs, and prognostic value landscape of glioma are remain unknown. Based on a wide variety of public databases and integrated several bioinformatics analysis methods, we evaluated expression dysregulations, clinical implications, DNA methylation, copy number alterations, prognostic and therapeutic values of CDCA family gene in glioma. Further, we identified crucial biomarker, CDCA2, that influence the progression of malignant glioma and poor prognosis. Thereafter, we disclosed the effect of CDCA2 knockdown on the biological function of glioma cells through various experiments in vitro. We found that the elevated mRNA expression of CDCAs in glioma. The upregulated expression of CDCAs was found to be associated with the tumor grade in glioma. The overexpression of CDCAs mRNA were correlated with the poor prognosis. Moreover, the expression level of CDCA2 was significantly higher in glioma, and the level is correlated with grade, age, IDH1 mutation and 1p19q codeletion states. Further cell experimental results supported that the ability of cell proliferation, migration, invasion and radioresistance of glioma cells was significantly decreased after downregulated CDCA2 expression, and these changes may be achieved through the RAD51 and p21/CDK2/CyclinE1 signaling pathways. These findings provide new insights into CDCAs from a bioinformatics standpoint and highlight the significance of CDCAs in glioma diagnosis and treatment. And knockdown of CDCA2 inhibits glioma cells' proliferation, migration, invasion and radioresistance. Regulation of CDCA2 on malignant progression of glioma cells may be realized through the RAD51 and p21/CDK2/CyclinE1 signaling pathways.

Hirudin inhibits glioma growth through mTOR-regulated autophagy.

Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose- and time-dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3-II but not Caspase-3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell-derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3-II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin-induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy.

Human neural stem cells repress glioma cell progression in a paracrine manner by downregulating the Wnt/β-catenin signalling pathway.

Neural stem cells (NSCs) play crucial roles in neurological disorders and tissue injury repair through exerting paracrine effects. However, the effects of NSC-derived factors on glioma progression remain unclear. This study aimed to evaluate the effects of human NSC-conditioned medium (NSC-CM) on the behaviour of glioma cells using an in vitro co-culture system. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays revealed that NSC-CM inhibited glioma cell proliferation and growth in a foetal bovine serum (FBS)-independent manner. In addition, our wound healing assay demonstrated that NSC-CM repressed glioma cell migration, while results from transwell and 3D spheroid invasion assays indicated that NSC-CM also reduced the invasion capacity of glioma cells. Flow cytometry showed that NSC-CM prevented cell cycle progression from the G1 to S phase and promoted apoptosis. Western blotting was used to show that the expression of Wnt/β-catenin pathway-related proteins, including β-catenin, c-Myc, cyclin D1, CD44, and Met, was remarkably decreased in NSC-CM-treated glioma cells. Furthermore, the addition of a Wnt/β-catenin pathway activator, CHIR99021, significantly induced the expression of β-catenin and Met and increased the proliferative and invasive capabilities of control medium-treated glioma cells but not those of NSC-CM-treated glioma cells. The use of enzyme-linked immunosorbent assays (ELISA) revealed the secretion of some anti-tumour factors in human and rat NSCs, including interferon-α and dickkopf-1. Our data suggest that NSC-CM partially inhibits glioma cell progression by downregulating Wnt/β-catenin signalling. This study may serve as a basis for developing future anti-glioma therapies based on NSC derivatives.

Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets.

Accumulating evidence supports that both long non-coding and micro RNAs (lncRNAs and miRNAs) are implicated in glioma tumorigenesis and progression. Poor outcome of gliomas has been linked to late-stage diagnosis and mostly ineffectiveness of conventional treatment due to low knowledge about the early stage of gliomas, which are not possible to observe with conventional diagnostic approaches. The past few years witnessed a revolutionary advance in biotechnology and neuroscience with the understanding of tumor-related molecules, including non-coding RNAs that are involved in the angiogenesis and progression of glioma cells and thus are used as prognostic biomarkers as well as novel therapeutic targets. The emerging research on lncRNAs and miRNAs highlights their crucial role in glioma progression, offering new insights into the disease. These non-coding RNAs hold significant potential as novel therapeutic targets, paving the way for innovative treatment approaches against glioma. This review encompasses a comprehensive discussion about the role of lncRNAs and miRNAs in gene regulation that is responsible for the promotion or the inhibition of glioma progression and collects the existing links between these key cancer-related molecules.