Guangyu Li

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-β-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 GSK3β mRNA of the Wnt-β-catenin pathway, activating it and consequently enhancing GBM malignancy. Conclusions: Our results demonstrate the PRMT6-YTHDF2-Wnt-β-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

Background Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Our current research finds PRMT6 upregulated in glioblastoma multiforme (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-β-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 GSK3β mRNA of the Wnt-β-catenin pathway, activating it and consequently enhancing GBM malignancy. Conclusions Our results demonstrate the PRMT6-YTHDF2-Wnt-β-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

Background: The homeobox gene 5 (HOXB5) encodes a transcription factor that regulates the embryonic development of the central nervous system. Notably, its expression pattern and prognostic role in glioma remain unelucidated. Methods: This study identified the relationship between HOXB5 and glioma by investigating HOXB5 expression data from The Cancer Genome Atlas and the Genotype Tissue Expression databases and validating the obtained data using the Chinese Glioma Genome Atlas database. Western blots were used to identify HOXB5 expression levels in glioma cells and clinical samples. Kaplan–Meier and multivariate Cox regression analyses were performed to assess the prognostic value of HOXB5. The key functions and signaling pathways related to HOXB5 were analyzed using GO, KEGG, and GSEA. Immune infiltration was calculated using the microenvironment cell populations-counter, estimate the proportion of immune and cancer, and ESTIMATE algorithms. Results: The expression of HOXB5 was upregulated in glioma and generally increased with malignancy. HOXB5 was an independent prognostic factor for glioma patients. A nomogram was further built that integrated HOXB5, and it showed stratifying prediction accuracy and efficiency. HOXB5 was associated with the regulation of cell growth, endothelial cell growth, and the IL-6/JAK-STAT3 pathway, and was determined to possibly promote stomatal specimen enrichment and angiogenesis. Conclusion: HOXB5 protein is overexpressed in glioma and might serve as a good predictive factor of this disease.

Background: Current treatment options for glioma are limited, and the prognosis of patients with glioma is poor as the available drugs show low therapeutic efficacy. Furthermore, the molecular mechanisms associated with glioma remain poorly understood. METTL1 mainly catalyzes the formation of N(7)-methylguanine at position 46 of the transfer RNA sequence, thereby regulating the translation process. However, the role of METTL1 in glioma has not been studied to date. The purpose of this study was to analyze the expression and prognosis of METTL1 in glioma, and to explore the potential analysis mechanism. Methods: Data from five publicly available databases were used to analyze METTL1 expression across different tumor types and its differential expression between carcinoma and adjacent normal tissues. The expression of METTL1 in glioma was further validated using real-time polymerase chain reaction and immunohistochemistry. Meanwhile, siRNA was used to knockdown METTL1 in U87 glioma cells, and the resultant effect on glioma proliferation was verified using the Cell Counting Kit 8 (CCK8) assay. Furthermore, a nomogram was constructed to predict the association between METTL1 expression and the survival rate of patients with glioma. Results: METTL1 expression increased with increasing glioma grades and was significantly higher in glioma than in adjacent noncancerous tissues. In addition, high expression of METTL1 promoted cell proliferation. Moreover, METTL1 expression was associated with common clinical risk factors and was significantly associated with the prognosis and survival of patients with glioma. Univariate and multivariate Cox regression analyses revealed that METTL1 expression may be used as an independent prognostic risk factor for glioma. Furthermore, results of functional enrichment and pathway analyses indicate that the mechanism of METTL1 in glioma is potentially related to the MAPK signaling pathway. Conclusions: High METTL1 expression is significantly associated with poor prognosis of patients with glioma and may represent a valuable independent risk factor. In addition, high expression of METTL1 promotes glioma proliferation and may regulate mitogen-activated protein kinase (MAPK) signaling pathway. Thus, METTL1 may be a potential biomarker for glioma. Further investigations are warranted to explore its clinical use.

Background: The homeobox gene 5 (HOXB5) encodes a transcription factor that regulates the central nervous system embryonic development. Of note, its expression pattern and prognostic role in glioma remain unelucidated. This study aimed to identify the relationship between HOXB5 and glioma by investigating the HOXB5 expression data from the The Cancer Genome Atlas (TCGA) and The Genotype Tissue Expression (GTEx) databases and validating the obtained data using the Chinese Glioma Genome Atlas (CGGA) database. Kaplan-Meier and univariate cox regression analyses were performed to assess the prognostic value of HOXB5. The key functions and signaling pathways of HOXB5 were analyzed using GSEA and GSVA. Immune infiltration was calculated using Microenvironment Cell Populations-counter (MCP-counter), single-sample Gene Set Enrichment Analysis (ssGSEA), and ESTIMATE algorithms.Result: HOXB5 expression was elevated in glioma tissues. The increased levels of HOXB5 were significantly correlated with a higher WHO grade and aggressive cancer phenotypes. HOXB5 overexpression represented a risk factor that was associated with shorter overall survival (OS) while exhibiting a moderate forecast efficiency in most clinical subgroups. These results were validated using the CGGA and Rembrandt datasets. Furthermore, the functional analysis showed enrichment of angiogenesis, the IL6/JAK-STAT3 pathway, and inflammatory response in the tissues that showed high expression of HOXB5. Lastly, the high expression of HOXB5 was associated with enrichment of Tregs and MDSCs, and HOXB5 expression was shown to play a role in several immune checkpoint genes.Conclusions: HOXB5 may serve as a predictive factor of glioma malignancy and prognostic status and represents potential as a molecular treatment candidate.

Background Glioma is characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, the prognosis of glioma is getting worse and worse with the increase of grade, which is not optimistic. Therefore, biological markers for glioma are needed in clinical to detect and evaluate the situation and prognosis of patients with glioma. In many studies, we have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors, which is associated with prognosis of patient. However, there has been no report or study on the role of PRMT6 in glioma. Methods In this study, we used various tumor-related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. Besides, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results PRMT6 is significantly differentially expressed in multiple tumors, which is associated with survival and prognosis. Especially in gliomas, the PRMT6 expression gradually increased with the grade increasing. Besides, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in various databases. Conclusions Our results indicate that high PRMT6 expression is a potential biomarker for predicting prognosis and progression of glioma.

Objectives: Free irons are transported into brain tissues by transferrin and play an important role in neuronal/glial cell damage. Lower serum levels of transferrin have been found in patients with ischemic stroke, compared with healthy subjects. In present study, we investigated whether transferrin unique peptide (TF-UP) could be employed as a serum biomarker for brain tissue damage in acute ischemic stroke.Methods: The venous blood samples of 94 ischemic stroke patients and 35 brain tumor-stroke mimics (BT-SM) patients were collected within the first 72 h (Median time 23.25, Interquartile range 60.75) of acute onset in the emergency room. Total TF-UP and total albumin unique peptide (Alb-UP) were identified with liquid chromatography/mass spectrometry (LC–MS/MS) and quantified by multiple reaction monitoring (MRM) method using labeled reference peptide (LRP) for further analysis.Results: Median ratio of total TF-UP/LRP was 0.85 (Interquartile range, 0.21) in the brain tumor-stroke mimics (BT-SM) group, and 0.45 (0.14) in the ischemic stroke group; median Alb-UP/LRP ratio was 0.66 (0.16) in the BT-SM group, and 0.55 (0.20) in the ischemic stroke group. The overall trend from low to high levels was statistically significant for TF-UP/LRP (P < 0.0001), but not for Alb-UP/LRP (P = 0.1667). According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9565 and the optimal cutoff value of serum TF-UP was 0.6317, which yielded a sensitivity of 91.49% and a specificity of 88.57%. The odds ratio (95% confidence intervals) of serum TF-UP/LRP was 83.31 (23.43, 296.22, P < 0.0001).Conclusions: Serum TF-UP/LRP level is decreased in patients with acute ischemic stroke in comparison with brain tumor, and it may serve as a serum biomarker for the neuronal/glial cell damage in cerebral infarction.

Background The primary features of malignant glioma include high rates of mortality and recurrence, uncontrollable invasiveness, strong angiogenesis, and widespread hypoxia. The hypoxic microenvironment is an important factor affecting the malignant progression of glioma. However, the molecular mechanisms underlying glioma adaption in hypoxic microenvironments are poorly understood. Objective The work presented in this paper focuses on the role of WNK3 gene in glioma invasion under hypoxic conditions. Furthermore, we aim to explore its role in epithelial-to-mesenchymal transition (EMT). Methods ShRNA targeting WNK3 transfection was used to knockdown the WNK3 expression in U87 cells. We used western blot analysis to detect the relative expression of proteins in U87 cells. The effect of WNK3 on cell migration was explored using a transwell assay in the U87 cell line. We also evaluated WNK3 expression levels in glioma samples by immunohistochemistry analysis. Results WNK3 expression was significantly higher in high-grade (III and IV) gliomas than in low-grade (I and II) gliomas. WNK3 expression was up-regulated in U87 cells when cultured in a hypoxic environment in addition; WNK3 knockdown inhibited the invasion of U87 glioma cells by regulating the EMT, especially under hypoxic conditions. Conclusion These findings suggested that WNK3 plays an important role in the hypoxic microenvironment of glioma and might also be a candidate for therapeutic application in the treatment of glioma.

Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.