PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt-ß-catenin pathway.

BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy. Yet, the specifics of PRMT6's regulatory processes and potential molecular mechanisms in GBM remain largely unexplored. METHODS: PRMT6's expression and prognostic significance in GBM were assessed using glioma public databases, immunohistochemistry (IHC), and immunoblotting. Scratch and Transwell assays examined GBM cell migration and invasion. Immunoblotting evaluated the expression of epithelial-mesenchymal transition (EMT) and Wnt-ß-catenin pathway-related proteins. Dual-luciferase reporter assays and ChIP-qPCR assessed the regulatory relationship between PRMT6 and YTHDF2. An in situ tumor model in nude mice evaluated in vivo conditions. RESULTS: Bioinformatics analysis indicates high expression of PRMT6 and YTHDF2 in GBM, correlating with poor prognosis. Functional experiments show PRMT6 and YTHDF2 promote GBM migration, invasion, and EMT. Mechanistic experiments reveal PRMT6 and CDK9 co-regulate YTHDF2 expression. YTHDF2 binds and promotes the degradation of negative regulators APC and GSK3ß mRNA of the Wnt-ß-catenin pathway, activating it and consequently enhancing GBM malignancy. CONCLUSIONS: Our results demonstrate the PRMT6-YTHDF2-Wnt-ß-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

The expanded endoscopic endonasal approach for treatment of tuberculum sellae meningiomas in a series of 40 consecutive cases.

Compared with traditional craniotomy, the expanded endoscopic endonasal approach (EEEA) may have some advantages for tuberculum sellae meningioma (TSM) treatment. We described our experience of the therapeutic effect of endoscopic TSM treatment. From August 2015 to December 2019, 40 patients with a TSM were treated by the EEEA in our institution. EEEA outcome in TSM treatment was analyzed. Among 39 patients with visual impairment, 38 (97.4%) improved their visual function to some extent after the EEEA, and one case had no significant change in visual acuity. Among all patients, 38 (95.0%) achieved gross total resection (GTR) and 2 (5.0%) achieved near-total resection (NTR). Cerebrospinal fluid (CSF) leakage occurred in three patients (7.5%) and meningitis (post-CSF leakage) in two patients (5.0%). Eight patients (20.0%) suffered postoperative hyposmia, three of whom developed long-term hyposmia. One patient (2.5%) suffered from bleeding of the branch of the anterior cerebral artery intraoperatively leading to postoperative acute cerebral infarction. The EEEA is a safe and reliable minimally invasive method for TSM removal. Compared with traditional craniotomy, the EEEA may have better visual outcomes and a higher prevalence of GTR, but carries the risk of CSF leakage.