Glioma Cell Invasion Research Articles

ZNF503-AS2 is a promising therapeutic target and is associated with the immune microenvironment in glioma.

Glioma is the most common intracranial malignancy, and the available treatment options are poor. Long noncoding RNAs (lncRNAs) have been reported to be involved in the malignant progression of glioma. The role of ZNF503-AS2 in glioma has not been reported. We screened ZNF503-AS2 with upregulated expression in glioblastoma (GBM) by analyzing the TCGA, CGGA and GTEx databases. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the enrichment of immune cells and signaling pathways in glioma samples. Single-cell datasets were used to analyze the distribution of ZNF503-AS2. In vitro experiments were used to investigate the biological function of ZNF503-AS2. ZNF503-AS2 was highly expressed in glioma and was associated with poor prognosis, malignant progression and infiltration of immunosuppressive cells. Single-cell transcriptomic analysis showed that ZNF503-AS2 was mainly expressed in macrophages and tumor cells. Further analysis revealed that immunotherapy may have better efficacy in patients with low ZNF503-AS2 expression. In vitro experiments showed that knockdown of ZNF503-AS2 reduced the proliferation, invasion and migration ability of glioma cells, induced G2/M cell cycle arrest and promoted apoptosis. ZNF503-AS2 might be a valuable biomarker for predicting the prognosis of glioma patients and a potential target for glioma therapy.

FAM3C Regulates Glioma Cell Proliferation, Invasion, Apoptosis, and Epithelial Mesenchymal Transition via the Notch Pathway.

Previous studies have implicated the involvement of FAM3C in cancerous development and progression. Herein, we aimed to further investigate the oncological mechanism of FAM3C, specifically in glioma. We utilized open-source bioinformatics tools and platforms to analyze the transcriptional expression levels, prognosis, and correlation with clinical variables of FAM3C in gliomas, and subsequently, to hypothesize its potential molecular functions and possibly associated signaling pathways. Following this, glioma tissues were obtained from resected specimens of patients to assess the expression of FAM3C and molecular markers related to epithelial-mesenchymal transition (EMT) and Notch signaling pathways. Furthermore, glioma cell lines were subjected to treatments including FAM3C siRNA knockdown, lentiviral overexpression, and Notch signaling pathway blockade, enabling the investigation of molecular functions of FAM3C invitro, particularly in EMT and Notch signaling pathways, as well as its effects on cancer cell proliferation, cell cycle progression, apoptosis, and invasion, using assays such as MMT cell proliferation assay, transwell migration, and flow cytometry analysis. Finally, a mouse subcutaneous xenograft model was established to explore the integrative function of FAM3C in glioma growth invivo. The expression level of FAM3C correlated with the progression of glioma grade and served as a prognostic indicator for poor patient outcomes. Subsequent experiments conducted on glioma cell lines, tumor tissues, and mouse models reinforced the close association of FAM3C with processes including glioma cell proliferation, cell cycle progression, apoptosis, and invasion. Additionally, it was observed that FAM3C is involved in the regulation of the Notch signaling pathway. FAM3C emerges as a potential candidate for clinical detection and prognostic biomarker application. Its regulatory role in glioma cell proliferation, cell cycle progression, and modulation of epithelial-mesenchymal transition-driven invasion and migration via the Notch signaling pathway implies its potential to unveil novel therapeutic targets for glioma treatment.

BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression.

Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain (BET) protein BRD4 in GBM, especially its interaction with immune checkpoints, is not well understood. Our study aimed to explore the role of BRD4 in GBM, especially the immune aspects. In this study, we performed bioinformatics gene expression and survival analysis of BRD4 using TCGA and CGGA databases. In addition, we investigated the effects of BRD4 on glioma cell proliferation, invasion and migration by clone formation assay, Transwell assay, CCK8 assay and wound healing assay. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. GL261 cells with BRD4 shRNA and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using H&E and IHC staining and immune cell infiltration were assessed by flow cytometry. The results showed that elevated expression of BRD4 in high-grade gliomas was associated with poor patient survival. In addition, we validated the promotional effects of BRD4 on glioma cell proliferation, invasion and migration. The results of ChIP experiments showed that BRD4 is a regulator of PD-L1 at the transcriptional level, implying that it is involved in the immune escape mechanism of glioma cells. In vivo studies showed that BRD4 knockdown inhibited tumor growth and reduced immunosuppression, improving prognosis. BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.

Research progress in the small G-protein Rac1

The small G-protein Rac1 is the main regulatory factor of the actin cytoskeleton. Rac1 cycles between the inactive GDP-bound form and the active GTP-bound form. Rac1 not only promotes viral replication and infection, but also regulates the actin cytoskeleton rearrangement, adhesion, and invasion of glioma cells. In addition, Rac1 is implicated in human diseases such as tumors and epilepsy. This article reviews the latest research on the small G-protein Rac1 in virology, cell biology, and human pathology. It is found that the existence of Rac1 is closely related to the replication and infection of viruses, that is, inhibiting the existence of Rac1 can effectively reduce the replication and transportation of viruses, providing new ideas for the development of various therapeutic drugs targeting Rac1.

Ribosomal protein S3A (RPS3A), as a transcription regulator of colony-stimulating factor 1 (CSF1), promotes glioma progression through regulating the recruitment and autophagy-mediated M2 polarization of tumor-associated macrophages.

Dysregulated expression of ribosomal protein S3A (RPS3A) is associated with the tissue infiltration of immune-related cells in a variety of cancers. However, the role of RPS3A in immune cell infiltration in glioma remains unclear. This study aimed to explore the role of RPS3A in the glioma immune microenvironment.RPS3A expression was detected in tumor tissues from patients with glioma. U251 cells were transfected with RPS3A shRNA (sh-RPS3A) and overexpression vector (pcDNA-RPS3A) and then co-cultured with PMA-induced THP-1 cells. Cell viability, invasion, and apoptosis were detected by Edu staining, Transwell, and flow cytometry, respectively. The expression of tumor-associated macrophage (TAM) M1 and M2 markers was detected with RT-qPCR. Next, the interaction between RPS3A and E4 transcription factor 1 (E4F1) was verified by Co-IP analysis, and the binding of E4F1 to colony-stimulating factor 1 (CSF1) promoter was verified by ChIP analysis. Overexpression vectors of CSF1 and E4F1 were used to treat sh-RPS3A-transfected U251 cells for reversal experiments. Finally, U251 cells transfected with sh-RPS3A adenovirus vectors were subcutaneously injected into nude mice to construct a xenograft tumor model, and the growth and metastasis of glioma in vivo were monitored.RPS3A was significantly upregulated in glioma tissues. Overexpression of RPS3A promoted glioma cell proliferation and invasion and inhibited apoptosis. Moreover, overexpression of RPS3A promoted TAM proliferation, invasion, and M2 polarization. Silencing RPS3A had the opposite effect. Silencing RPS3A inhibited autophagy in U251 cells, whereas rapamycin, an activator of autophagy, reversed the inhibitory effect of RPS3A silencing on TAM M2 polarization. Meanwhile, RPS3A promoted its expression by interacting with E4F1, and E4F1 promoted CSF1 transcriptional activation. Overexpression of CSF1 promoted the proliferation and invasion of U251 cells and reversed the inhibitory effect of RPS3A silencing on TAM proliferation and invasion, but had no effect on TAM M2 polarization. The results of in vivo experiments showed that knockdown of RPS3A significantly inhibited glioma tumor growth and metastasis in vivo.This study revealed that RPS3A recruited TAMs by upregulating E4F1-mediated transcription activation of CSF1, and promoted the M2 polarization of TAMs through autophagy, promoting glioma cell malignant growth and tumor progression.

TMIC-38. INTEGRIN BLOCKING PEPTIDE REPROGRAMS THE IMMUNOSUPPRESSIVE MICROENVIRONMENT OF EXPERIMENTAL GLIOMAS IMPROVING ANTI-PD-1 THERAPY OUTCOME

Abstract Clinical trials with immune checkpoint inhibitors (ICI) have benefited many cancer patients but failed in a number of tumors, including glioblastoma (GBM), the most common and aggressive primary brain tumor in adults. The main obstacle for ICI efficacy in GBM is the continuously evolving tumor microenvironment (TME), in which antitumor immunity is inhibited or eluded by tumor-secreted factors. Accumulation and reprogramming of myeloid cells (GAMs) creates a “cold” immunosuppressive TME with a poor infiltration and exhaustion of effector T cells. We employ Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) with 40 protein markers along with spatial transcriptomics and immunophenotyping to dissect identities and functionalities of immune cells (CD45+) in experimental GL261 gliomas. The results revealed identities of immune cells instrumental for creating the immunosuppressive milieu and cell-cell communication networks. We have developed a designer RGD peptide that blocks the reprogramming of GAMs by targeting tumor-GAMs interactions. We demonstrate that RGD efficiently blocks microglia-dependent invasion of murine and human glioma cells in vitro. We explored if the intratumorally delivered RGD can revert tumor-induced changes in the TME of experimental gliomas and improve anti-PD-1 immunotherapy. While RGD alone did not reduce tumor growth in vivo, it prevented reprogramming of myeloid cells into protumoral GAMs and led to the normalization of peritumoral blood vessels. Combining RGD with anti-PD-1 antibody resulted in reduced tumor growth, increase in percentages of proliferating, interferon-ɣ producing CD8+T cells and depletion of regulatory T cells. Transcriptomic profiles of GAMs were altered by the combined treatment, consistently with the restored “hot” inflammatory TME which resulted in boosting immunotherapy responses. Intratumorally delivered RGD modified in the same way functionalities of GAMs in the TME of human U87MG gliomas in nude mice. Our results demonstrate that the integrin blockade combined with immune checkpoint inhibitors reinvigorates both innate and adaptive antitumor immunity. The results pave the way to improve responses to immunotherapy in GBM and other cancers.

EZH2 Promotes Glioma Cell Proliferation, Invasion, and Migration via Mir-142-3p/KCNQ1OT1/HMGB3 Axis : Running Title: EZH2 Promotes Glioma cell Malignant Behaviors.

This study investigates the role and molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration. EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 expressions in glioma tissues and cells were determined using qRT-PCR or Western blot, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability. A nude mouse xenograft model and a lung metastasis model were established. EZH2, KCNQ1OT1, LIN28B, and HMGB3 were highly expressed while miR-142-3p was poorly expressed in gliomas. EZH2 silencing restrained glioma cell proliferation, invasion, and migration. EZH2 repressed miR-142-3p expression by elevating the H3K27me3 level. miR-142-3p targeted KCNQ1OT1 expression, and KCNQ1OT1 bound to LIN28B to stabilize HMGB3 mRNA, thereby promoting its protein expression. EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. In conclusion, EZH2 curbed miR-142-3p expression, thereby relieving the inhibition of KCNQ1OT1 expression by miR-142-3p, enhancing the binding of KCNQ1OT1 to LIN28B, elevating HMGB3 expression, and ultimately accelerating glioma cell proliferation, invasion, and migration.

Kinin Receptors B1 and B2 Mediate Breast Cancer Cell Migration and Invasion by Activating the FAK-Src Axis.

Kinin receptors B1 and B2 are involved in migration and invasion in gastric, glioma, and cervical cancer cells, among others. However, the role of kinin receptors in breast cancer cells has been poorly studied. We aimed to reveal the impact of B1 and B2 receptors on migration and invasion in breast cancer cells and demonstrate their capacity to modulate in vivo tumor growth. MDA-MB-231, MCF-7, and T47D cells treated with Lys-des[Arg9]bradykinin (LDBK) or bradykinin (BK) were used to evaluate migration and invasion. Des-[Arg9]-Leu8-BK and HOE-140 were used as antagonists for the B1 and B2 receptors. MDA-MB-231 cells incubated or not with antagonists were subcutaneously inoculated in BALBc NOD/SCID mice to evaluate tumor growth. LDBK and BK treatment significantly increased migration and invasion in breast cancer cells, effects that were negated when antagonists were used. The use of antagonists in vivo inhibited tumor growth. Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK-Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth.

Integrated analysis of bulk and single-cell RNA sequencing reveals the impact of nicotinamide and tryptophan metabolism on glioma prognosis and immunotherapy sensitivity

BackgroundNicotinamide and tryptophan metabolism play important roles in regulating tumor synthesis metabolism and signal transduction functions. However, their comprehensive impact on the prognosis and the tumor immune microenvironment of glioma is still unclear. The purpose of this study was to investigate the association of nicotinamide and tryptophan metabolism with prognosis and immune status of gliomas and to develop relevant models for predicting prognosis and sensitivity to immunotherapy in gliomas.MethodsBulk and single-cell transcriptome data from TCGA, CGGA and GSE159416 were obtained for this study. Gliomas were classified based on nicotinamide and tryptophan metabolism, and PPI network associated with differentially expressed genes was established. The core genes were identified and the risk model was established by machine learning techniques, including univariate Cox regression and LASSO regression. Then the risk model was validated with data from the CGGA. Finally, the effects of genes in the risk model on the biological behavior of gliomas were verified by in vitro experiments.ResultsThe high nicotinamide and tryptophan metabolism is associated with poor prognosis and high levels of immune cell infiltration in glioma. Seven of the core genes related to nicotinamide and tryptophan metabolism were used to construct a risk model, and the model has good predictive ability for prognosis, immune microenvironment, and response to immune checkpoint therapy of glioma. We also confirmed that high expression of TGFBI can lead to an increased level of migration, invasion, and EMT of glioma cells, and the aforementioned effect of TGFBI can be reduced by FAK inhibitor PF-573,228.ConclusionsOur study evaluated the effects of nicotinamide and tryptophan metabolism on the prognosis and tumor immune microenvironment of glioma, which can help predict the prognosis and sensitivity to immunotherapy of glioma.

Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review.

Tryptophan is widely present in foods such as peanuts, milk, and bananas, playing a crucial role in maintaining metabolic homeostasis in health and disease. Tryptophan metabolism is involved in the development and progression of immune, nervous, and digestive system diseases. Although some excellent reviews on tryptophan metabolism exist, there has been no systematic scientometric study as of yet. This review provides and summarizes research hotspots and potential future directions by analyzing annual publications, topics, keywords, and highly cited papers sourced from Web of Science spanning 1964 to 2022. This review provides a scientometric overview of tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies. The gut microbiota regulates gut permeability, inflammation, and host immunity by directly converting tryptophan to indole and its derivatives. Gut microbial metabolites regulate tryptophan metabolism by activating specific receptors or enzymes. Additionally, the kynurenine (KYN) pathway, activated by indoleamine-2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase, affects the migration and invasion of glioma cells and the development of COVID-19 and depression. The research and development of IDO inhibitors help to improve the effectiveness of immunotherapy. Tryptophan metabolites as potential markers are used for disease therapy, guiding clinical decision-making. Tryptophan metabolites serve as targets to provide a new promising strategy for neuroprotective/neurotoxic imbalance affecting brain structure and function. In summary, this review provides valuable guidance for the basic research and clinical application of tryptophan metabolism.

Retracted] Rab5 regulates the proliferation, migration and invasion of glioma cells via cyclin E.

[This retracts the article DOI: 10.3892/ol.2020.11660.].

Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma

BackgroundAs part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined.MethodsImmunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method.Results IER3was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group.ConclusionsIn this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.

Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF‑κB signaling pathway.

Frizzled family protein 2 (FZD2) is widely associated with tumor development and metastasis. The present study aimed to gain an insight into the role and regulatory mechanism of FZD2 in glioma. The expression level of FZD2 in normal astrocyte and glioma cells was determined by reverse transcription-quantitative PCR and western blotting, and cell transfection was conducted for FZD2 expression knockdown. Malignant behaviors including cell proliferation, migration and invasion, vasculogenic mimicry (VM) and cell stemness were determined using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU) staining, colony formation, wound healing, Transwell, 3D culturing and sphere formation assays. The expression levels of proteins related to stemness, epithelial-mesenchymal transition (EMT) and Notch/NF-κB signaling were measured by western blotting. Then, the Notch agonist, Jagged-1 (JAG), was adopted for rescue experiments. The results demonstrated that FZD2 was highly expressed in glioma cells. Interference of FZD2 expression suppressed the proliferation of glioma cells, as evidenced by the reduced cell viability and the number of EdU+ cells and colonies. Meanwhile, the reduced sphere formation ability and decreased protein expression of Nanog, Sox2 and Oct4 following FZD2 knockdown confirmed that FZD2 repressed cell stemness in glioma. Additionally, FZD2 knockdown suppressed the migration, invasion, EMT and VM formation capabilities of glioma cells, and also blocked the Notch/NF-κB signaling pathway. Furthermore, activation of Notch by JAG treatment partially reversed the aforementioned FZD2 knockdown-mediated changes in glioma cell malignant behaviors. In conclusion, FZD2 may contribute to glioma progression through activating the Notch/NF-κB signaling pathway, providing a plausible therapeutic target for the treatment of glioma.

Regulation of a novel circATP8B4/miR-31-5p/nestin ceRNA crosstalk in proliferation, motility, invasion and radiosensitivity of human glioma cells.

Deregulation of circular RNAs (circRNAs) is frequent in human glioma. Although circRNA ATPase phospholipid transporting 8B4 (circATP8B4) is highly expressed in glioma, its precise action in glioma development is still not fully understood. The relationship of microRNA (miR)-31-5p and circATP8B4 or nestin (NES) was predicted by bioinformatic analysis and confirmed by RNA pull-down and Dual-luciferase reporter assays. CircATP8B4, miR-31-5p and NES were quantified by qRT-PCR or western blot. Cell functional behaviors were assessed by EdU, wound-healing and transwell invasion assays. Xenograft model experiments were performed to define circATP8B4's activity in vivo. CircATP8B4, a true circular transcript, was upregulated in human glioma. CircATP8B4 downregulation weakened glioma cell growth, motility, and invasion and facilitated radiosensitivity. Mechanistically, circATP8B4 and NES 3'UTR harbored a shared miR-31-5p pairing site, and circATP8B4 involved the post-transcriptional NES regulation by functioning as a competing endogenous RNA (ceRNA). Furthermore, the miR-31-5p/NES axis participated in circATP8B4's activity in glioma cell proliferation, motility, invasion and radiosensitivity. Additionally, circATP8B4 loss diminished tumor growth and enhanced the anticancer effect of radiotherapy in vivo. We have uncovered an uncharacterized ceRNA cascade, circATP8B4/miR-31-5p/NES axis, underlying glioma development and radiosensitivity. Targeting the ceRNA crosstalk may have potential to improve the outcome of glioma patients.

Research progress on platelets in glioma.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.

Invasiveness modulation of glioma cells by copper complex-loaded nanoarchitectures

Among the tumors with the highest lethality, gliomas are primary brain tumors associated with common recurrence inclined to metastasize along the neuraxis and occasionally out of the central nervous system. Even though metastasis is the main responsible for death in oncological patients, few dedicated treatments are approved. Therefore, the establishment of effective anti-metastasis agents is the final frontier in cancer research. Interestingly, some copper complexes have demonstrated promising efficacy as antimetastatic agents, but they may cause off-site effects such as the alteration of copper homeostasis in healthy tissues. Thus, the incorporation of copper-based antimetastatic agents in rationally designed nano-architectures can increase the treatment localization reducing the side effects. Here, copper complex loaded hybrid nano-architectures (CuLNAs) are presented and employed to assess the impact of an intracellular copper source on glioma cell invasiveness. The novel CuLNAs are fully characterized and exploited for cell migration modulation in a glioma cell line. The results demonstrate that CuLNAs significantly reduce cell migration without impairing cell proliferation compared to standard gold and copper NAs. A concomitant antimigratory-like regulation of the epithelial-to-mesenchymal transition genes confirmed these results, as the gene encoding for the epithelial protein E-cadherin was upregulated and the other explored mesenchymal genes were downregulated. These findings, together with the intrinsic behaviors of NAs, demonstrate that the inclusion of metal complexes in the nano-architectures is a promising approach for the composition of a family of agents with antimetastatic activity.

Exploring the multifaceted role of key lncRNA in glioma: From genetic expression to clinical implications and immunotherapy potential

BackgroundLong non-coding RNAs (lncRNAs) are implicated in a variety of regulatory functions within tumors, yet their specific roles in glioma remain underexplored. MethodsWe extracted glioma patient data from The Cancer Genome Atlas and UCSC Xena database for analysis using R, focusing on genomic characterization, biological enrichment, immune evaluation, and the development of a predictive model employing machine learning techniques. Additionally, we conducted cell culture and proliferation assays. ResultsOur analysis revealed that the lncRNA SLC16A1-AS1 plays a pivotal role in glioma pathogenesis and prognosis. We observed that abnormal expression of SLC16A1-AS1 varied with tumor grade, IDH mutation status, and histological type, correlating with worse survival outcomes. Genomically, SLC16A1-AS1 was associated with Tumor Mutational Burden and other prognostic biomarkers. The expression of this lncRNA was also linked to the activation of critical biological pathways and appeared to modulate the immune microenvironment, enhancing the presence of immune cells and checkpoints, which may be predictive of immunotherapy outcomes. Our predictive model, constructed from genes associated with SLC16A1-AS1, accurately forecasted glioma prognosis, strongly correlating with survival and treatment responses. In vitro experiments further demonstrated that SLC16A1-AS1 significantly influences glioma cell proliferation, invasion, and migration, underscoring its role in tumor aggression and its potential as a therapeutic target. ConclusionsThis study underscores the significant influence of SLC16A1-AS1 on glioma progression and prognosis, with its expression correlating with tumor traits and immune responses. The findings highlight the potential of targeting SLC16A1-AS1 in therapeutic strategies aimed at mitigating glioma aggressiveness.

Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography.

Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion. Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE). Experimental, animal model. Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice). 2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength). Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology. Paired and unpaired t-tests, a P-value ≤0.05 was considered significant. From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10-6 mm2/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression. MRE is promising for the assessment of key glioma characteristics. NA TECHNICAL EFFICACY: Stage 2.

NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation

Nuclear regulation has potential in cancer therapy, with the nuclear pore complex (NPC) serving as a critical channel between the nucleus and cytoplasm, playing a role in regulating various biological processes and cancer. DNA methylation, an epigenetic modification mediated by DNA methyltransferases (DNMTs), influences gene expression and cell differentiation, and is crucial for the development and progression of tumor cells. Gliomas are the most common primary brain tumors, with glioblastoma being particularly aggressive, characterized by invasiveness, migration capability, and resistance to conventional treatments, resulting in poor prognosis. Our study revealed that the expression level of NUP37 affects the proliferation and invasion of glioma cells, and that the overexpression of DNMT1 can alleviate the adverse effects caused by NUP37 depletion. These findings suggest that NUP37 promotes the proliferation and invasion of glioma cells through its interaction with DNMT1.

Increased UBD Is a Potential Diagnostic and Prognostic Biomarker in Glioma.

Various studies have demonstrated that ubiquitin D (UBD) is overexpressed in different cancer types and may serve as a potential prognostic factor. However, additional research is necessary to establish the prognostic significance and possible role of UBD in glioma. Transcriptomic expression data from The Cancer Genome Atlas database (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed to identify UBD expression differences in tumor and normal tissues. The relative levels of UBD in glioma and normal tissues were determined using qRT-PCR and WB. Logistic regression analysis was performed to investigate the association between UBD expression and clinicopathological characteristics of glioma patients. To evaluate the diagnostic and prognostic predictive values of UBD, we used Kaplan-Meier survival curves, Cox regression analysis, diagnostic receiver operating characteristic (ROC) curves, and nomogram model. We also conducted wound healing assays, transwell assays, EdU assays, and colony formation assays to verify the UBD function. Gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as gene set enrichment analysis (GSEA), were employed to determine the functions of UBD. Finally, we performed the western blot assays to assess changes in EMT markers as well as p-PI3K, p-AKT, and p-mTOR expressions. Our study revealed a remarkable increase of UBD expression in glioma samples. Cox regression analysis demonstrated that high expression of UBD mRNA was an independent prognostic factor for overall survival (OS) in TCGA. ROC curve analysis showed that UBD expression levels could differentiate glioma from adjacent normal tissues accurately. Additionally, knockdown of UBD reduced the migration, invasion, and proliferation ability of glioma cells while UBD overexpression had the opposite effect. GSEA showed that the expression of UBD involved with various pathways including epithelial-mesenchymal transition (EMT), PI3K-AKT-mTOR signaling, P53 pathway, angiogenesis, inflammatory response, KRAS signaling, hypoxia, as well as TGF-β signaling. Furthermore, our findings suggest that UBD accelerates the activation of EMT and PI3K/AKT/mTOR pathway.