最近的研究强调了 NF-κB 信号通路在癌症发生和进展中的重要作用。此外，长非编码 RNA (lncRNA) 已被确定为维持 NF-κB 信号通路功能的关键调节因子。尽管有这些发现，lncRNA 影响 NF-κB 通路的潜在分子机制在很大程度上仍未被探索。利用生物信息学分析来研究 XTP6 的差异表达和预后意义。通过体外和体内实验方法进一步阐明了 XTP6 的功能作用。为了评估 XTP6 和 NDH2 之间的相互作用，进行了 RNA Pulldown 和 RNA 免疫沉淀 (RIP) 测定。使用 RNA 纯化染色质分离 (ChIRP) 测定法检查 XTP6 和 IκBα 启动子之间的连接。此外，还进行了染色质免疫沉淀 (ChIP) 分析，以分析 c-myc 与 XTP6 启动子的结合亲和力，从而深入了解发挥作用的调节机制。XTP6 在多形性胶质母细胞瘤 (GBM) 组织中显着上调，并与不良预后相关GBM 患者。我们的研究表明，XTP6 在体外和体内均可促进 GBM 的恶性进展。此外，XTP6 通过将 NDH2 招募到 IκBα 启动子来下调 IκBα 表达，从而导致 H3K27me3 水平升高，从而降低 IκBα 的转录活性。此外，c-myc 介导的 XTP6 上调进一步驱动 GBM 的进展，与 IκBα 建立正反馈环，从而永久激活 NF-κB 信号通路。值得注意的是，针对 NF-κB 信号通路的抑制剂的应用有效抑制了 XTP6 诱导的持续激活，从而显着减少了体内肿瘤的形成。结果表明，XTP6 揭示了一种创新的表观遗传机制，有助于持续激活 XTP6。 NF-κB 信号通路，提出了治疗 GBM 的一个有前景的治疗靶点。© 2024。作者。

Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway's functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored.Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play.XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo.The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.© 2024. The Author(s).