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Glioblastoma multiforme (GBM) is a significantly malignant and lethal brain tumor with an average survival time of less than 12 months. Several researches had shown that Claudin-3 (CLDN3) is overexpressed in various cancers and might be important in their growth and spread. In this study, we used qRT-PCR, western blotting, immunohistochemistry, and immunofluorescence staining assays to investigate the expression levels of various proteins. To explore the proliferation abilities of GBM cells, we conducted the CCK-8 and EdU-DNA formation assays. Wound healing and transwell assays were used to investigate the capacities of invasion and migration of GBM cells. Additionally, we constructed an intracranial xenograft model of GBM to study the in vivo role of CLDN3. Our study devoted to investigate the function of CLDN3 in the pathogenesis and progression of GBM. Our study revealed that CLDN3 was upregulated in GBM and could stimulate tumor cell growth and epithelial-mesenchymal transition (EMT) in both laboratory and animal models. We also discovered that CLDN3 expression could be triggered by transforming growth factor-β (TGF-β) and reduced by specific inhibitors of the TGF-β signaling pathway, such as ITD-1. Further analysis revealed that increased CLDN3 levels enhanced TGF-β-induced growth and EMT in GBM cells, while reducing CLDN3 levels weakened these effects. Our study demonstrated the function of CLDN3 in facilitating GBM growth and metastasis and indicated its involvement in the tumorigenic effects of TGF-β. Developing specific inhibitors of CLDN3 might, therefore, represent a promising new approach for treating this devastating disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As in many other cancers, highly malignant proliferation and disordered cell division play irreplaceable roles in the exceedingly easy recurrence and complex progression of glioblastoma multiforme (GBM); however, mechanistic studies of the numerous regulators involved in this process are still insufficiently thorough. The role of BCAS3 has been studied in other cancers, but its role in GBM is unclear. Here, our goal was to investigate the expression pattern of BCAS3 in GBM and its potential mechanism of action. Using TCGA database and human GBM samples, we found that BCAS3 expression was up-regulated in GBM, and its high expression predicted poor prognosis. To further investigate the relationship between BCAS3 and GBM characteristics, we up-regulated and down-regulated BCAS3 expression in GBM to detect its effect on cell proliferation and cell cycle. At the same time, we established U87 cells stably overexpressing BCAS3 and generated an intracranial xenograft model to investigate the Potential role of BCAS3 in vivo. Finally, based on in vitro cell experiments and in vivo GBM xenograft models, we observed that BCAS3 significantly regulates GBM cell proliferation and cell cycle and that this regulation is associated with p53/GADD45α Signaling pathway. Taken together, our findings suggest that BCAS3 is inextricably linked to the progression of GBM and that targeting BCAS3 may have therapeutic effects in GBM patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. The unregulated expression of Claudin-4 (CLDN4) plays an important role in tumor progression. However, the biological role of CLDN4 in GBM is still unknown. This study aimed to determine whether CLDN4 mediates glioma malignant progression, if so, it would further explore the molecular mechanisms of carcinogenesis. Our results revealed that CLDN4 was significantly upregulated in glioma specimens and cells. The inhibition of CLND4 expression could inhibit mesenchymal transformation, cell invasion, cell migration and tumor growth in vitro and in vivo. Moreover, combined with in vitro analysis, we found that CLDN4 can modulate tumor necrosis factor-α (TNF-α) signal pathway. Meanwhile, we also validated that the transforming growth factor-β (TGF-β) signal pathway can upregulate the expression of CLDN4, and promote the invasion ability of GBM cells. Conversely, TGF-β signal pathway inhibitor ITD-1 can downregulate the expression of CLDN4, and inhibit the invasion ability of GBM cells. Furthermore, we found that TGF-β can promote the nuclear translocation of CLDN4. In summary, our findings indicated that the TGF-β/CLDN4/TNF-α/NF-κB signal axis plays a key role in the biological progression of glioma. Disrupting the function of this signal axis may represent a new treatment strategy for patients with GBM., (© 2022. The Author(s).)

In this study, we demonstrate that bone mesenchymal stem cell (BMSC)-derived exosomes alter tumor phenotypes by delivering miR-512-5p. miR-512-5p was downregulated in glioblastoma tissues and cells, and Jagged 1 (JAG1) was the target gene of miR-512-5p. We clarified the expression patterns of miR-512-5p and JAG1 along with their interactions in glioblastoma. Additionally, we observed that BMSC-derived exosomes could contain and transport miR-512-5p to glioblastoma cells in vitro . BMSC-derived exosomal miR-512-5p inhibited glioblastoma cell proliferation and induced cell cycle arrest by suppressing JAG1 expression. In vivo assays validated the in vitro findings, with BMSC-exosomal miR-512-5p inhibiting glioblastoma growth and prolonging survival in mice. These results suggest that BMSC-derived exosomes transport miR-512-5p into glioblastoma and slow its progression by targeting JAG1. This study reveals a new molecular mechanism for glioblastoma treatment and validates miRNA packaging into exosomes for glioblastoma cell communication.

The most common and aggressive type of brain cancer in adults is glioblastoma multiforme (GBM), and hypoxia is a common feature of glioblastoma. As the histological features of glioma include capillary endothelial cell proliferation, they are highly prone to invading the surrounding normal brain tissue, which is often one of the reasons for the failure of treatment. However, the mechanisms involved in this process are not fully understood. MicroRNAs (miRs) are a class of non‑coding RNA that are able to inhibit the malignant progression of tumor cells through the regulation of downstream genes. In the present study, the low expression of miR‑576‑3p was detected in glioma samples and hypoxia‑treated glioma cells using a reverse transcription‑quantitative polymerase chain reaction. The present study focused on the effects of miR‑576‑3p on hypoxia‑induced glioma. The results of the functional experiments revealed that the overexpression of miR‑576‑3p significantly inhibited the migration and pro‑angiogenic abilities of the glioma cells under hypoxic conditions (P<0.05) compared with in the lentivirus‑miR‑negative control group. Furthermore, luciferase reporter gene assays were used to validate the hypothesis that miR‑576‑3p interacts with the 3'‑untranslated region of hypoxia‑inducible factor‑1α (HIF‑1α) and induces a reduction in the protein levels of matrix metalloproteinase‑2 and vascular endothelial growth factor. Rescue experiments demonstrated that the restoration of HIF‑1α expression attenuated the effect of miR‑576‑3p on the migration and proangiogenic abilities of glioma cells. In conclusion, the present study confirms that miR‑576‑3p is a novel GBM inhibitor and its inhibition of the migration and proangiogenic capacity of hypoxia‑induced glioma cells is mediated by HIF‑1α.