Wang Changyu, He Yan, Fang Xiang, Zhang Danyang, Huang Jinhai, Zhao Shuxin, Li Lun, Li Guangyu
Department of Neurosurgery, The First Hospital of China Medical University, NO. 155 Nanjing North Street, Heping District, Shenyang 110002, China.
Department of Laboratory Animal Science, China Medical University, 110122, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, P.R. China.
iScience. 2024 Jun 8;27(7):110225. doi: 10.1016/j.isci.2024.110225. eCollection 2024 Jul 19.
Glioblastoma (GBM) is characterized by aggressive growth, invasiveness, and poor prognosis. Elucidating the molecular mechanisms underlying GBM is crucial. This study explores the role of Sm-like protein 14 homolog A (LSM14A) in GBM. Bioinformatics and clinical tissue samples analysis demonstrated that overexpression of LSM14A in GBM correlates with poorer prognosis. CCK8, EdU, colony formation, and transwell assays revealed that LSM14A promotes proliferation, migration, and invasion in GBM . mouse xenograft models confirmed the results of the experiments. The mechanism of LSM14A modulating GBM cell proliferation was investigated using mass spectrometry, co-immunoprecipitation (coIP), protein half-life, and methylated RNA immunoprecipitation (MeRIP) analyses. The findings indicate that during the G1/S phase, LSM14A stabilizes DDX5 in the cytoplasm, regulating CDK4 and P21 levels. Furthermore, METTL1 modulates LSM14A expression via mRNA mG methylation. Altogether, our work highlights the METTL1-LSM14A-DDX5 pathway as a potential therapeutic target in GBM.
胶质母细胞瘤（GBM）具有生长侵袭性强和预后差的特点。阐明GBM潜在的分子机制至关重要。本研究探讨了类Sm蛋白14同源物A（LSM14A）在GBM中的作用。生物信息学和临床组织样本分析表明，GBM中LSM14A的过表达与较差的预后相关。CCK8、EdU、集落形成和Transwell实验表明，LSM14A促进GBM的增殖、迁移和侵袭。小鼠异种移植模型证实了实验结果。使用质谱、免疫共沉淀（coIP）、蛋白质半衰期和甲基化RNA免疫沉淀（MeRIP）分析研究了LSM14A调节GBM细胞增殖的机制。研究结果表明，在G1/S期，LSM14A在细胞质中稳定DDX5，调节CDK4和P21水平。此外，METTL1通过mRNA mG甲基化调节LSM14A的表达。总之，我们的研究突出了METTL1-LSM14A-DDX5通路作为GBM潜在治疗靶点的作用。
