ArticleNeuro-oncology2024
Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 30 citations in OpenAlex.
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofInfection and immunity · 2026Article
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.MedScience · 2026Article
- Status and trends in glioblastoma lipid metabolism research: a bibliometric analysis.Discover oncology · 2026Review
- LRP2-mediated regulation of ferroptosis through the Wnt/β-catenin-GPX4 axis in colorectal cancer liver metastasis and chemoresistance.Cell death discovery · 2026Article
- B7-H3 interaction with cMet enhances lipolysis to drive malignant progression of glioma via pSTAT3-ATGL axis.Journal of translational medicine · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- SREBF2 enhances lipid metabolism and represses anti-tumor immune responses in cervical cancer by increasing ACAT2.Communications biology · 2026Article
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- IGF2BP3-dependent glutamine/BCAA metabolic rewiring rejuvenates aged human adipose-derived stem cells for enhanced tissue regeneration.Cell discovery · 2026Article
- Comprehensive pan-cancer analysis and experimental verification of the roles of SCP2 in colon adenocarcinoma.BMC cancer · 2026Article
- HNRNPA2B1 as an emerging coordinator of RNA fate in cancer: m6A reading, RNA export, translation reprogramming, and immune-metabolic adaptation.Frontiers in immunology · 2026Review
- SREBP2-activated CNPY3 Phase Separation Promotes Colorectal Cancer by Enhancing MDM2-mediated p53 Degradation.International journal of biological sciences · 2026Article
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofbioRxiv : the preprint server for biology · 2025Article
- mActa pharmaceutica Sinica. B · 2025Review
- Emerging role of RNA m6A modifications in laryngeal squamous cell carcinoma: insights into tumorigenesis and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Review
- Review
- Development of a prognostic model based on m6A readerTranslational cancer research · 2025Article
- Copy number amplification of TTPAL promotes cholesterol biosynthesis and esophageal squamous cell carcinoma progression via elevating NSUN2-mediated m5C modification of SREBP2 mRNA.Journal of experimental & clinical cancer research : CR · 2025Article
- The dual role of RNA-binding proteins: promotion of tumorigenesis, drug resistance, and emerging therapeutic targets.Acta biochimica et biophysica Sinica · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDysregulation of cholesterol metabolism is a significant characteristic of glioma, yet the underlying mechanisms are largely unknown. N6-methyladenosine (m6A) modification has been implicated in promoting tumor development and progression. The aim of this study was to determine the key m6A regulatory proteins involved in the progression of glioma, which is potentially associated with the reprogramming of cholesterol homeostasis.
methodsBioinformatics analysis was performed to determine the association of m6A modification with glioma malignancy from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Glioma stem cell (GSC) self-renewal was determined by tumor sphere formation and bioluminescence image assay. RNA sequencing and lipidomic analysis were performed for cholesterol homeostasis analysis. RNA immunoprecipitation and luciferase reporter assay were performed to determine hnRNPA2B1-dependent regulation of sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR) mRNA. The methylation status of hnRNPA2B1 promoter was determined by bioinformatic analysis and methylation-specific PCR assay.
resultsAmong the m6A-regulatory proteins, hnRNPA2B1 was demonstrated the most important independent prognostic risk factor for glioma. hnRNPA2B1 ablation exhibited a significant tumor-suppressive effect on glioma cell proliferation, GSC self-renewal and tumorigenesis. hnRNPA2B1 triggers de novo cholesterol synthesis by inducing HMGCR through the stabilization of SREBP2 mRNA. m6A modification of SREBP2 or LDLR mRNA is required for hnRNPA2B1-mediated mRNA stability. The hypomethylation of cg21815882 site on hnRNPA2B1 promoter confers elevated expression of hnRNPA2B1 in glioma tissues. The combination of targeting hnRNPA2B1 and cholesterol metabolism exhibited remarkable antitumor effects, suggesting valuable clinical implications for glioma treatment.
conclusionshnRNPA2B1 facilitates cholesterol uptake and de novo synthesis, thereby contributing to glioma stemness and malignancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.