Target For Glioma Therapy Research Articles

PEGylated Nanoliposomal Doxorubicin Conjugated with Specific TREM2 Peptides for Glioma-Targeting Therapy.

PEGylated liposomes can deliver anti-cancer drugs to brain tumors, and achieve enhanced permeability and retention effects. Triggering receptor expressed on myeloid cells 2 (TREM2) is an excellent biomarker for precise therapyof glioma. The present study is aimed at designing PEGylatednanoliposomal doxorubicin (PLD) conjugated with peptides targeting TREM2 for glioma-targeting therapy. The specific peptides are designed with the Rosetta Peptiderive Protocol. Schrodinger's peptide-specific version of Glide is used for molecular docking.PLD modified with peptides (peptide-PLD) are engineered and prepared. Cell cycle, apoptosis, cell invasion and migration, cell viability, and colony-formation assays are performed to analyze glioma cell functions. The anti-tumor effects of peptide-PLD are validated in an intracranial U87-MG cells orthotopic glioma model. The targeting peptides HLRKLRKR and LRKLRLRL showed specific affinity for TREM2 and better cellular uptake in U87-MG cells. PLD with peptide modification demonstrated stable doxorubicin loading, small sizes (<60nm), and enrichment in the mouse brain. Peptide-PLD treatment inhibited the Akt/GSK3β/β-catenin pathway, thereby inhibiting cell invasion and migration, and colony-forming ability in U87-MG cells. The peptide modification of PLD achieved better suppression of glioma development than PLD.Overall, TREM2-targeting peptides are successfully designed, and peptide-PLD served as a potent drug delivery carrier for glioma-targeting therapy.

Enhancing glioblastoma cytotoxicity through encapsulating O6-benzylguanine and temozolomide in PEGylated liposomal nanocarrier: an in vitro study

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (−49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC50 value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

Advances in Targeted Glioma Therapy with Transferrin-Conjugated Gemcitabine-Loaded PLGA Nanoparticles

Advances in Targeted Glioma Therapy with Transferrin-Conjugated Gemcitabine-Loaded PLGA Nanoparticles

TCAF2 drives glioma cellular migratory/invasion properties through STAT3 signaling

Glioma is an intracranial tumor characterized by high mortality and recurrence rates. In the present study, the association of TRPM8 channel-associated factor 2 (TCAF2) in glioma was investigated using bioinformatics, showing significant relationships with age, WHO grade, IDH, and 1p/19q status, as well as being an independent predictor of prognosis. Immunohistochemistry of a glioma sample microarray showed markedly increased TCAF2 expression in glioblastoma relative to lower-grade glioma, with elevated expression predominating in the tumor center. Raised TCAF2 levels promote glioma cell migratory/invasion properties through the epithelial-to-mesenchymal transition-like (EMT-like) process, shown by Transwell and scratch assays and western blotting. It was further found that the effects of TCAF2 were mediated by the activation of STAT3. These results suggest that TCAF2 promotes glioma cell migration and invasion, rendering it a potential drug target in glioma therapy.

Targeted glioma therapy makes strides

Targeted glioma therapy makes strides

STAT1 negatively regulates human glioma U251 cell proliferation Huang et al: Role of STAT1 in glioma

Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.

Advances in antibody-based drugs and their delivery through the blood-brain barrier for targeted therapy and immunotherapy of gliomas.

Gliomas are highly invasive and are the most common type of primary malignant brain tumor. The routine treatments for glioma include surgical resection, radiotherapy, and chemotherapy. However, glioma recurrence and patient survival remain unsatisfactory after employing these traditional treatment approaches. With the rapid development of molecular immunology, significant breakthroughs have been made in targeted glioma therapy and immunotherapy. Antibody-based therapy has excellent advantages in treating gliomas due to its high specificity and sensitivity. This article reviewed various targeted antibody drugs for gliomas, including anti-glioma surface marker antibodies, anti-angiogenesis antibodies, and anti-immunosuppressive signal antibodies. Notably, many antibodies have been validated clinically, such as bevacizumab, cetuximab, panitumumab, and anti-PD-1 antibodies. These antibodies can improve the targeting of glioma therapy, enhance anti-tumor immunity, reduce the proliferation and invasion of glioma, and thus prolong the survival time of patients. However, the existence of the blood-brain barrier (BBB) has caused significant difficulties in drug delivery for gliomas. Therefore, this paper also summarized drug delivery methods through the BBB, including receptor-mediated transportation, nano-based carriers, and some physical and chemical methods for drug delivery. With these exciting advancements, more antibody-based therapies will likely enter clinical practice and allow more successful control of malignant gliomas.

Tumoricidal, Temozolomide- and Radiation-Sensitizing Effects of KCa3.1 K+ Channel Targeting In Vitro Are Dependent on Glioma Cell Line and Stem Cell Fraction.

Reportedly, the intermediate-conductance Ca2+-activated potassium channel KCa3.1 contributes to the invasion of glioma cells into healthy brain tissue and resistance to temozolomide and ionizing radiation. Therefore, KCa3.1 has been proposed as a potential target in glioma therapy. The aim of the present study was to assess the variability of the temozolomide- and radiation-sensitizing effects conferred by the KCa3.1 blocking agent TRAM-34 between five different glioma cell lines grown as differentiated bulk tumor cells or under glioma stem cell-enriching conditions. As a result, cultures grown under stem cell-enriching conditions exhibited indeed higher abundances of mRNAs encoding for stem cell markers compared to differentiated bulk tumor cultures. In addition, stem cell enrichment was paralleled by an increased resistance to ionizing radiation in three out of the five glioma cell lines tested. Finally, TRAM-34 led to inconsistent results regarding its tumoricidal but also temozolomide- and radiation-sensitizing effects, which were dependent on both cell line and culture condition. In conclusion, these findings underscore the importance of testing new drug interventions in multiple cell lines and different culture conditions to partially mimic the in vivo inter- and intra-tumor heterogeneity.

CSIG-40. STEAROYL-COA DESATURASE 1 (SCD1) IS REQUIRED FOR WNT SIGNALING TO INDUCE AN APOPTOSIS IN IDH MUTANT GLIOMA

Abstract BACKGROUND AND HYPOTHESES SCD1, a major enzyme of saturated fatty acids, has been implicated to be important for tumor metabolic reprograming. Our previous study show that a high level of SCD1 mRNA is associated with IDH1mut lower grade gliomas. IDH1mut glioma cells are more sensitive to SFA induced apoptosis. However, the underlying mechanism remains unclear. In this study, we investigate the functions of SCD1 in IDHmut glioma and the potential contribution of SCD1 for cancer therapy of glioma. STUDY DESIGN AND METHODS The genetically engineered IDH wild-type, IDHmut and patient derived glioma cell lines were used to evaluate SCD1 functions. The expression of proteins were checked by Western-blotting assay. SCD1 was silenced by CRISPR or siRNA. The transcriptome change after SCD1 knockdown was profiled by RNA-seq or single cell RNA-seq (scRNA-seq). RESULTS AND CONCLUSIONS SCD1 transient silencing slowed down the cell growth, suggesting that SCD1 may possess an oncogenic property. RNA-seq analysis revealed that SCD1 inhibition decreased the expression of wnt-signaling pathway genes in IDH-1mut cells. scRNA confirmed that CRISPR SCD1 significantly decreased wnt signaling in the patient cell line Ts603. Therefore, we activated wnt pathway using a small chemical compound, BML-2838. Consistent with recent studies, wnt pathway induction led to a dramatically suppression of glioma cells growth. However, SCD1 silencing reversed this inhibitory effect. Further investigation revealed that SCD1 inhibition reduced the nucleus translocation of phosphorylated beta-catenin. Overall, the results suggest that SCD1 is vital for the onset of wnt pathway in glioma cells. High level of SCD1 expression may render the IDHmut glioma cells more sensitive to wnt pathway induced apoptosis. RELEVANCE AND IMPORTANCE In clinical, the 5-years survival rate of glioma remains low. SCD1 have been considered as a target for glioma therapy, recently. Our data provides a new insight on the strategy to target SCD1 in clinical.

Prefoldin 6 promotes glioma progression via the AKT signalling pathway.

Gliomas are one of the most aggressive primary tumours, accounting for 81% of malignant brain tumours, and are associated with a significant mortality. Therefore, the elucidation of the molecular mechanism underlying glioma progression and identification of promising treatment targets are necessary. Here, the expression of prefoldin (PFDN) 6 in human glioma tissues and cell lines was evaluated using immunohistochemistry and quantitative polymerase chain reaction. Celigo and CCK-8 assays were performed for assessing cell viability. Flow cytometry was used to analyse apoptosis and cell cycle distribution. Wound-healing and transwell assays were performed to observe cell migration. Lastly, xenograft models were developed for the in vivo validation of the results, and a human phospho-kinase array was used to explore the downstream signalling pathways. PFDN6 was upregulated in gliomas, and PFDN6 overexpression was significantly correlated with a low survival rate, estimated glomerular filtration rate (EGFR) expression, and tumour grade and recurrence. Moreover, PFDN6 knockdown significantly attenuated cell proliferation and migration, induced apoptosis, and blocked cell cycle progression in the G2 phase, which was further confirmed in the in vivo experiments. Mechanistically, the effects of PFDN6 may be mediated via the AKT signalling pathway. In conclusion, we showed that PFDN6 promotes glioma development by activating AKT signalling and emphasised the potential of PFDN6 as a crucial target in glioma therapy.

KLHDC8A Expression in Association with Macrophage Infiltration and Oxidative Stress Predicts Unfavorable Prognosis for Glioma.

Background The tumor immune microenvironment (TME) is associated with cancer progression and immune escape. Although KLHDC8A has been reported in glioma in vitro, the expression and clinical significance of this gene in clinical samples are unknown. Methods The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to evaluate the mRNA expression level of KLHDC8A and its significance in the glioma TME. Tissue microarray-based multiple immunohistochemical staining was conducted to determine KLHDC8A protein levels and characterize the immune signature of tumor-infiltrating immune cells in gliomas. Results Tumor cells and tumor-associated macrophages expressed KLHDC8A. The expression of KLHDC8A was higher in glioma tissues than in normal brain tissues and was associated with patient clinical characteristics. Gliomas exhibited a high abundance of macrophages, neutrophils, regulatory T cells, and the immune checkpoint PD-L1, as well as high KLHDC8A expression. Cox regression analysis showed that KLHDC8A+CD68+ macrophages and KLHDC8A predicted unfavorable survival in patients with glioma. Finally, protein-protein interaction network analysis showed that the KLHDC8A expression was associated with hypoxia and oxidative stress. Conclusions KLHDC8A is a potential marker for the clinical diagnosis of glioma. The immune characteristics of macrophages play a crucial role in predicting patients with glioma, providing a new avenue for targeted glioma therapy.

MiR-133a-5p Inhibits Glioma Cell Proliferation by Regulating IGFBP3.

Objective This research aims to investigate the expression of miR-133a-5p in glioma tissues and its impact on glioma cell proliferation. Methods Fluorescence-quantitative PCR was used to detect the expression of miR-133a-5p in 25 cases of glioma and adjuncent tissues. CCK-8 and colony formation analyses were used to evaluate the impact of transfection with miR-133a-5p inhibitors or mimics on glioma cell growth and colony formation. The IGFBP3 (insulin-like growth factor-binding protein-3) and miR-133a-5p binding sites were predicted using Starbase, and the miR-133a-5p binding capacity with 3'UTR of IGFBP3 gene was determined using a luciferase gene reporter system. Following transfection with miR-133a-5p mimics or inhibitors, the IGFBP3 protein expression in glioma cells was determined by western blotting. The colony formation assay was applied to evaluate the influence of IGFBP3 overexpression on the miR-133a-5p in glioma cell proliferation. For assessment of the IGFBP3 expression in glioma tissues and prognosis, TCGA database was employed. Results The expression of miR-133a-5p was considerably reduced in glioma tissue compared to adjuncent control tissue. In addition, miR-133a-5p expression decreased with increasing glioma malignancy. Glioma cell growth and colony formation were reduced after miR-133a-5p mimics were transfected, while transfection of miR-133a-5p inhibitors had a reverse impact. The expression of IGFBP3 was affected by miR-133a-5p by binding to its 3'UTR region. Additional study demonstrated that the overall survival (OS) of subjects with increased IGFBP3 expression was considerably lower compared to patients with decreased IGFBP3 expression. The IGFBP3 overexpression effectively counteracts the glioma cell proliferation-inhibiting impact of miR-133a-5p. Conclusion miR-133a-5p acts as a glioma tumor suppressor gene. It reduces glioma cell proliferation by modulating IGFBP3 and could be a target for glioma therapy.

LCS-1 inhibition of superoxide dismutase 1 induces ROS-dependent death of glioma cells and degradates PARP and BRCA1.

Gliomas are characterized by high morbidity and mortality, and have only slightly increased survival with recent considerable improvements for treatment. An innovative therapeutic strategy had been developed via inducing ROS-dependent cell death by targeting antioxidant proteins. In this study, we found that glioma tissues expressed high levels of superoxide dismutase 1 (SOD1). The expression of SOD1 was upregulated in glioma grade III and V tissues compared with that in normal brain tissues or glioma grade I tissues. U251 and U87 glioma cells expressed high levels of SOD1, low levels of SOD2 and very low levels of SOD3. LCS-1, an inhibitor of SOD1, increased the expression SOD1 at both mRNA and protein levels slightly but significantly. As expected, LCS-1 caused ROS production in a dose- and time-dependent manner. SOD1 inhibition also induced the gene expression of HO-1, GCLC, GCLM and NQO1 which are targeting genes of nuclear factor erythroid 2-related factor 2, suggesting the activation of ROS signal pathway. Importantly, LCS-1 induced death of U251 and U87 cells dose- and time-dependently. The cell death was reversed by the pretreatment of cells with ROS scavenges NAC or GSH. Furthermore, LCS-1 decreased the growth of xenograft tumors formed by U87 glioma cells in nude mice. Mechanistically, the inhibition of P53, caspases did not reverse LCS-1-induced cell death, indicating the failure of these molecules involving in cell death. Moreover, we found that LCS-1 treatment induced the degradation of both PARP and BRCA1 simultaneously, suggesting that LCS-1-induced cell death may be associated with the failure of DNA damage repair. Taking together, these results suggest that the degradation of both PARP and BRCA1 may contribute to cell death induced by SOD1 inhibition, and SOD1 may be a target for glioma therapy.

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas.

Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell–cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immune-related pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.

HOTAIRM1 Maintained the Malignant Phenotype of tMSCs Transformed by GSCs via E2F7 by Binding to FUS.

Objective Mesenchymal stromal/stem cells (MSCs) are an important part of the glioma microenvironment and are involved in the malignant progression of glioma. In our previous study, we showed that MSCs can be induced to a malignant phenotype (tMSCs) by glioma stem cells (GSCs) in the microenvironment. However, the potential mechanism by which tMSCs maintain their malignant phenotype after malignant transformation has not been fully clarified. Methods The expression of HOTAIRM1, FUS, and E2F7 was detected by qRT-PCR. Clone formation, EdU, and Transwell assay were used to explore the role of HOTAIRM1, FUS, and E2F7 on the proliferation, migration, and invasion of tMSCs. Bioinformatics analysis and RNA immunoprecipitation were used to explore the relation among HOTAIRM1, FUS, and E2F7. Results HOTAIRM1 was upregulated in tMSCs compared with MSCs. Loss- and gain-of-function assays showed that HOTAIRM1 promoted the proliferation, migration, and invasion of tMSCs. qRT-PCR and functional assays revealed that E2F7 might be the downstream target of HOTAIRM1. A further study of the mechanism showed that HOTAIRM1 could bind to FUS, an RNA-binding protein (RBP), and thus regulate E2F7, which could promote the malignant phenotype of tMSCs. Conclusion Our study revealed that the HOTAIRM1/FUS/E2F7 axis is involved in the malignant progression of tMSCs transformed by GSCs in the glioma microenvironment and may function as a novel target for glioma therapy.

Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN

Macrophage-derived exosomes (Mφ-Exos) are involved in tumor progression, but its role in glioma is not fully understood. RBP-J is related to macrophage activation. In this study, we assess the role of exosomes derived from RBP-J-overexpressed macrophages (RBP-J OE Mφ-Exos) in glioma. The circular RNA (circRNA) profiles in RBP-J OE Mφ-Exos and THP-1-like macrophages (WT Mφ)-Exos were evaluated using circRNA microarray. Then the functions of Mφ-Exo-circRNA in glioma cells were assessed via CCK-8, EdU, Transwell invasion, and nude mouse assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson’s correlation analysis were adopted to confirm interactions. We found that circRNA BTG (circBTG2) is upregulated in RBP-J OE Mφ-Exos compared to WT Mφ-Exos. RBP-J OE Mφ-Exos co-culture and circBTG2 overexpression inhibited proliferation and invasion of glioma cells, whereas circBTG2 knockdown promotes tumor growth in vivo. The effects of RBP-J OE Mφ-Exos on glioma cells can be reversed by the circBTG2 knockdown. In conclusions, Exo-circBTG2 secreted from RBP-J OE Mφ inhibits tumor progression through the circBTG2/miR-25-3p/PTEN pathway, and circBTG2 is probably a diagnostic biomarker and potential target for glioma therapy.

High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML.

Glioma stem cells (GSCs) are critical targets for glioma therapy. SOX9 is a transcription factor with critical roles during neurodevelopment, particularly within neural stem cells. Previous studies showed that high levels of SOX9 are associated with poor glioma patient survival. SOX9 knockdown impairs GSCs proliferation, confirming its potential as a target for glioma therapy. In this study, we characterized the function of SOX9 directly in patient-derived glioma stem cells. Notably, transcriptome analysis of GSCs with SOX9 knockdown revealed STAT3 and PML as downstream targets. Functional studies demonstrated that SOX9, STAT3, and PML form a regulatory loop that is key for GSC activity and self-renewal. Analysis of glioma clinical biopsies confirmed a positive correlation between SOX9/STAT3/PML and poor patient survival among the cases with the highest SOX9 expression levels. Importantly, direct STAT3 or PML inhibitors reduced the expression of SOX9, STAT3, and PML proteins, which significantly reduced GSCs tumorigenicity. In summary, our study reveals a novel role for SOX9 upstream of STAT3, as a GSC pathway regulator, and presents pharmacological inhibitors of the signaling cascade.

Erythrocyte-cancer Hybrid Membrane-camouflaged Mesoporous Silica Nanoparticles Loaded with Gboxin for Glioma-targeting Therapy.

The purpose of this research is to formulate a biomimetic drug delivery system, which can selectively target glioblastoma (GBM) to deliver the antitumor agent, Gboxin, a novel Complex V inhibitor. Gboxin can specifically inhibit GBM cell growth but not normal cells. In the present study, we utilized red blood cell (RBC) membrane and U251 cell membrane to obtain a hybrid biomimetic membrane (RBC-U), and prepared RBC-U coated Gboxin-loaded mesoporous silica nanoparticles ((MSNs/Gboxin)@[RBC-U]) for GBM chemotherapy. The zeta potential, particle size, and morphology of (MSNs/Gboxin)@[RBC-U] were characterized. The cellular uptake, effect of cells growth inhibition, biocompatibility, and specific self-recognition of nanoparticles were evaluated. The (MSNs/Gboxin)@[RBC-U] was successfully fabricated and possessed high stability in the circulation system. The drug loading of Gboxin was 13.9%. (MSNs/Gboxin)@ [RBC-U] could effectively retain drugs in the physiological environment and released Gboxin rapidly in the tumor cells. Compared to the MSNs/Gboxin, the (MSNs/Gboxin)@[RBC-U] exhibit highly specific self-recognition to the source cell line. Additionally, the (MSNs/Gboxin) @[RBC-U] showed excellent anti-proliferation efficiency (IC50 = 0.21 μg/mL) in the tumor cell model and few side effects in normal cels in vitro. The (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effects in vitro and the specific self-recognition to GBM cells. Hence, (MSNs/Gboxin)@[RBC-U] could be a promising delivery system for GBM targeted therapy.

LOXL1-AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR-374b-5p/MMP14 axis.

At present, growing evidence indicates that long non‐coding RNAs (lncRNAs) participate in the progression of glioma. The function of LOXL1‐AS1 in vasculogenic mimicry (VM) in glioma remains unclear. First, the expressions of TIAR, the lncRNA LOXL1‐AS1, miR‐374b‐5p and MMP14 were examined by qRT‐PCR and Western blot in both, glioma tissues and glioma cell lines. Proliferation, migration, invasion and tube formation assays were conducted to evaluate the roles of TIAR, LOXL1‐AS1, miR‐374b‐5p and MMP14 in malignant cellular behaviours in glioma cells. A nude mouse xenograft model and dual staining for CD34 and PAS were used to assess whether VM was affected by TIAR, LOXL1‐AS1 or miR‐374b‐5p in vivo. In this study, low levels of TIAR and high levels of LOXL1‐AS1 were found in glioma cells and tissues. TIAR downregulated the expression of LOXL1‐AS1 by destabilizing it. LOXL1‐AS1 acted like a miRNA sponge towards miR‐374b‐5p so that downregulation of the former greatly inhibited cell proliferation, migration, invasion and VM. Additionally, miR‐374b‐5p overexpression repressed malignant biological behaviours and VM in glioma by modifying MMP14. In summary, we demonstrated that TIAR combined with LOXL1‐AS1 modulates VM in glioma via the miR‐374b‐5p/MMP14 axis, revealing novel targets for glioma therapy.

Limb-bud and heart development (LBH) contributes to glioma progression in vitro and in vivo.

Glioma is the predominant brain malignancy and is correlated with high mortality and severe morbidity. The transcription factor limb‐bud and heart (LBH) has been reported to be involved in the development of several cancers, although its role in glioma development remains elusive. Here, we examined the effect of LBH on glioma progression. The expression of LBH was increased in glioma samples from The Cancer Genome Atlas database, and upregulation of LBH was observed to be correlated with the poor survival of glioma patients. We also report that expression of LBH was elevated in clinical glioma tissues compared to adjacent normal tissues, and was also enhanced in glioma cell lines. LBH promotes proliferation and inhibits cell cycle arrest and apoptosis in glioma cells. In addition, LBH increased the migration and invasion of glioma cells in vitro. Moreover, tumorigenicity analysis revealed that LBH could promote the tumor growth of glioma cells in vivo. In conclusion, our findings suggest that LBH contributes to glioma progression in vitro and in vivo. Our findings provide new insights into the mechanism by which LBH promotes the development of glioma, improving our understanding of the correlation between LBH with cancer. LBH may have potential as a target for glioma therapy.