m5C 修饰的 LINC00324 通过 CBX3/VEGFR2 通路促进胶质瘤血管生成。
m5C modification of LINC00324 promotes angiogenesis in glioma through CBX3/VEGFR2 pathway.
机构信息
Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.
Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.; Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
出版信息
Int J Biol Macromol. 2024 Feb;257(Pt 1):128409. doi: 10.1016/j.ijbiomac.2023.128409. Epub 2023 Nov 26.
Angiogenesis plays a major role in tumor initiation, progression, and metastasis. This is why finding antiangiogenic targets is essential in the treatment of gliomas. In this study, NSUN2 and LINC00324 were significantly upregulated in conditionally cultured glioblastoma endothelial cells (GECs). Knockdown of NSUN2 or LINC00324 inhibits GECs angiogenesis. NSUN2 increased the stability of LINC00324 by m5C modification and upregulated LINC00324 expression. LINC00324 competes with the 3'UTR of CBX3 mRNA to bind to AUH protein, reducing the degradation of CBX3 mRNA. In addition, CBX3 directly binds to the promoter region of VEGFR2, enhances VEGFR2 transcription, and promotes GECs angiogenesis. These findings demonstrated NSUN2/LINC00324/CBX3 axis plays a crucial role in regulating glioma angiogenesis, which provides new strategies for glioma therapy.
血管生成在肿瘤的发生、进展和转移中起着重要作用。这就是为什么寻找抗血管生成靶点在治疗神经胶质瘤中至关重要。在这项研究中，条件培养的神经胶质瘤内皮细胞（GEC）中 NSUN2 和 LINC00324 显著上调。敲低 NSUN2 或 LINC00324 抑制 GEC 血管生成。NSUN2 通过 m5C 修饰增加 LINC00324 的稳定性并上调 LINC00324 的表达。LINC00324 与 CBX3 mRNA 的 3'UTR 竞争结合 AUH 蛋白，从而降低 CBX3 mRNA 的降解。此外，CBX3 直接结合 VEGFR2 的启动子区域，增强 VEGFR2 的转录，促进 GEC 血管生成。这些发现表明 NSUN2/LINC00324/CBX3 轴在调节神经胶质瘤血管生成中起着关键作用，为神经胶质瘤治疗提供了新策略。
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