HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner.

Glioma is the most common malignant tumor in the central nervous system, and it is crucial to uncover the factors that influence prognosis. In this study, we utilized Mfuzz to identify a gene set that showed a negative correlation with overall survival in patients with glioma. Gene Ontology (GO) enrichment analyses were then undertaken to gain insights into the functional characteristics and pathways associated with these genes. The expression distribution of Hyaluronan Synthase 2 (HAS2) was explored across multiple datasets, revealing its expression patterns. In vitro and in vivo experiments were carried out through gene knockdown and overexpression to validate the functionality of HAS2. Potential upstream transcription factors of HAS2 were predicted using transcriptional regulatory databases, and these predictions were experimentally validated using ChIP-PCR and dual-luciferase reporter gene assays. The results showed that elevated expression of HAS2 in glioma indicates poor prognosis. HAS2 was found to play a role in activating an antiferroptosis pathway in glioma cells. Inhibiting HAS2 significantly increased cellular sensitivity to ferroptosis-inducing agents. Finally, we determined that the oncogenic effect of HAS2 is mediated by the key receptor of the WNT pathway, FZD7.

The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma.

BACKGROUND: Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression. METHODS: Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2. CONCLUSION: Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.

Global analysis of iron metabolism-related genes identifies potential mechanisms of gliomagenesis and reveals novel targets.

AIMS: This study aimed to investigate key regulators of aberrant iron metabolism in gliomas, and evaluate their effect on biological functions and clinical translational relevance. METHODS: We used transcriptomic data from multiple cross-platform glioma cohorts to identify key iron metabolism-related genes (IMRGs) based on a series of bioinformatic and machine learning methods. The associations between IMRGs and prognosis, mesenchymal phenotype, and genomic alterations were analyzed in silico. The performance of the IMRGs-based signature in predicting temozolomide (TMZ) treatment sensitivity was evaluated. In vitro and in vivo experiments were used to explore the biological functions of these key IMRGs. RESULTS: HMOX1, LTF, and STEAP3 were identified as the most essential IMRGs in gliomas. The expression levels of these genes were strongly related to clinicopathological and molecular features. The robust IMRG-based gene signature could be used for prognosis prediction. These genes facilitate mesenchymal transformation, driver gene mutations, and oncogenic alterations in gliomas. The gene signature was also associated with TMZ resistance. HMOX1, LTF, and STEAP3 knockdown in glioma cells significantly reduced cell proliferation, colony formation, migration, and malignant invasion. CONCLUSION: The study presented a comprehensive view of key regulators underpinning iron metabolism in gliomas and provided new insights into novel therapeutic approaches.

Skull base reconstruction using in situ bone flap in patients with pituitary adenomas treated by endoscopic endonasal approach.

Objective: The objective of this study is to study the effect of in situ bone flap (ISBF) repositioning, a recently proposed rigid skull base reconstruction technique, on patients diagnosed with pituitary adenoma undergoing endoscopic endonasal approach (EEA). Method: A retrospective analysis was conducted on 188 patients with pituitary adenomas who underwent EEA from February 2018 to September 2022. Patients were divided into the ISBF group and non-ISBF group, according to whether ISBF was used during skull base reconstruction. Results: Of the 75 patients in the non-ISBF group, 6 had postoperative cerebrospinal fluid (CSF) leakage (8%), while only 1 of 113 patients in the ISBF group (0.8%) had postoperative CSF leakage, indicating that the incidence of postoperative CSF leakage in the ISBF group was significantly lower than that in the non-ISBF group (P = 0.033). In addition, we also found that the postoperative hospitalization days of patients in the ISBF group (5.34 ± 1.24) were significantly less than those in the non-ISBF group (6.83 ± 1.91, P = 0.015). Conclusion: ISBF repositioning is a safe, effective, and convenient rigid skull base reconstruction method for patients with pituitary adenoma treated by EEA, which can significantly reduce the rate of postoperative CSF leakage and shorten postoperative hospital stays.

Application of dural suturing in the endoscopic endonasal approach to the sellar region.

Objectives: The endoscopic endonasal approach (EEA) is widely used in the treatment of cranial base tumors. Skull base reconstruction is a crucial part of EEA, which has a great impact on patients' prognosis. In this study, we report our experience with sellar dural suturing in cranial base reconstruction and retrospectively analyze its effect. Methods: The clinical data of 134 patients who suffered intraoperative CSF leakage and underwent EEA surgery in the Department of Neurosurgery of the First Affiliated Hospital of Nanjing Medical University from October 2018 to November 2020 were retrospectively collected and analyzed. According to whether sellar dural suturing was performed during the operation, they were divided into a suture group (55 cases) and a control group (79 cases). Results: The results showed that dural suturing of the sellar floor effectively reduced the postoperative hospitalization duration (p = 0.026) and the use rates of lumbar drainage (p = 0.047), autologous fat transplantation (p = 0.038), and pedicled nasoseptal flaps (p = 0.026). Conclusion: Sellar dural suturing under endoscopy is a promising and effective method for cranial base reconstruction in EEA surgery and is worthy of clinical application.