Integrative Analysis Identifies NSUN2 as an Essential Coordinator for Glioma Malignancy and Glucose Metabolism

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-12-03 DOI:10.1002/jgm.70004

Yuze He, Yunbo Yuan, Linzi Ji, Yuting Shu, Zhihao Wang, Shuxin Zhang, Wanchun Yang, Mina Chen, Yanhui Liu

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Abstract

Background

Glioma, particularly glioblastoma, is the most common and aggressive primary brain tumor, with poor prognosis due to its metabolic heterogeneity. NSUN2, an m5C RNA methyltransferase and direct glucose sensor, has been implicated in various malignancies, but its role in glioma remains unclear.

Methods

Bioinformatic analysis was performed on multiple public databases and our glioma dataset from West China Hospital (WCH). In vitro experiments were conducted to assess the effects of NSUN2 knockdown on glioma cell proliferation, migration, and chemotherapeutic sensitivity. Transcriptomic analysis was employed to obtain mechanistic insights.

Results

NSUN2 expression was significantly upregulated in gliomas and correlated with higher tumor grade and poor prognosis. NSUN2 knockdown reduced glioma cell proliferation, migration, and increased sensitivity to temozolomide. Transcriptomic analysis revealed that NSUN2 knockdown downregulated key genes involved in glioma progression. Mechanistically, NSUN2 positively regulates the activity of mTORC1 signaling, as indicated by phosphorylated S6 ribosomal protein and 4EBP1. Moreover, NSUN2 overexpression reciprocally increased tumor volume compared with controls, indicating NSUN2 promoting glioma cell proliferation in vivo.

Conclusions

Our findings highlight NSUN2 as a critical regulator of glioma malignancy. Targeting NSUN2 disrupts key pathways in glioma progression, suggesting it as a promising therapeutic target. Our work underscores the potential of NSUN2 inhibition to enhance treatment efficacy and improve patient outcomes in glioma.

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.