长非编码RNA（lncRNA）调节复杂疾病和癌症的发病机制，包括胶质母细胞瘤（GBM）。然而，基于lncRNA的治疗因许多lncRNA与其结合伴侣的作用机制不完全了解而受到限制。我们使用转录组和基因组数据分析LINC02283与PDGFRA（血小板来源性生长因子受体A）之间的相关性。利用患者源性胶质瘤干细胞（GSCs）和正交移植的GBM裸鼠模型，评估了新型lncRNA的生物学功能。通过免疫印迹（IB）、qRT-PCR、RNA pull down、交联RNA免疫沉淀（CL-RIP）、荧光原位杂交和ASO介导的敲低，探究了LINC02283对PDGFRA信号的调控作用。利用病理诊断的GBM患者样本评估了LINC02283的表达。我们发现一种新的致癌性lncRNA，LINC02283，在PDGFRA突变驱动的胶质瘤患者组中高度表达，并与更差的预后相关。LINC02283基因共扩增PDGFRA位点，并与PDGFRA表达高度相关。在具有PDGFRA扩增突变的GSCs中剥夺LINC02283会减弱其肿瘤生成能力并增强正交移植GBM模型的生存率，而在具有野生型PDGFRA的GSCs中过表达LINC02283会增强PDGFRA信号传导并降低生存率。此外，LINC02283与PDGFRA相互作用以增强其信号以及其下游目标AKT和ERK的信号，从而促进GBM的肿瘤发生。我们的研究结果提供了LINC02283作为PDGFRA致癌活性和GBM恶性的调节因子的强有力证据，并支持lncRNA作为潜在治疗靶点的可能性。© 作者（们）2023年。由牛津大学出版社代表神经肿瘤学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

Long non-coding RNAs (lncRNAs) regulate the etiology of complex diseases and cancers, including glioblastoma (GBM). However, lncRNA-based therapies are limited because the mechanisms of action of many lncRNAs with their binding partners are not completely understood.We used transcriptomic and genomic data to analyze correlations between LINC02283 and PDGFRA (Platelet derived growth factor receptor A). The biological functions of the novel lncRNA were assessed in vivo using patient-derived glioma stem-like cells (GSCs), and orthotopic GBM xenografts. Immunoblotting (IB), qRT-PCR, RNA pull down, crosslinked RNA immunoprecipitation (CL-RIP), fluorescence in situ hybridization and ASO-mediated knockdown were performed to explore the regulation of LINC02283 on PDGFRA signaling. Expression of LINC02283 in clinical samples was assessed using pathologically diagnosed GBM patient samples.We identified a novel oncogenic lncRNA, LINC02283, that is highly expressed in the PDGFRA-mutation driven cohort of glioma patients and associated with worse prognosis. LINC02283 gene co-amplifies with the PDGFRA locus and shows high correlation with PDGFRA expression. Deprivation of LINC02283 in GSCs with PDGFRA amplification mutation, attenuated tumorigenicity and enhanced survival in orthotopic GBM xenograft models, while overexpression of LINC02283 in GSCs with wild type-PDGFRA, enhances PDGFRA signaling, and decreases survival. Further, LINC02283 interacts with PDGFRA to enhance its signaling and that of its downstream targets AKT and ERK, thus promoting oncogenesis in GBM.Our results provide strong evidence of LINC02283 as a regulator of PDGFRA oncogenic activity and GBM malignancy and support the potential of lncRNAs as possible therapeutic targets.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.