lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation
lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation
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lncRNA RMST 通过增强 FUS SUMOylation 抑制 GBM 细胞线粒体自噬
DOI：
10.1016/j.omtn.2020.01.008
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发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Wu, Minghua
中科院分区：
文献类型：
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作者：
Liu, Changhong;Peng, Zixuan;Wu, Minghua
长非编码 RNA (lncRNA) 在蛋白质翻译后修饰中发挥重要作用，但 lncRNA 对于 SUMO 化的重要性尚不清楚。通过定量实时 PCR 和原位杂交测量神经胶质瘤组织和正常脑组织中横纹肌肉瘤 2 相关转录本 (RMST) 的表达。一系列体外实验证明了 RMST 在星形细胞瘤中的功能作用。通过 RNA 免疫沉淀、RNA Pulldown、蛋白质印迹和免疫共沉淀测定研究了 RMST 的 SUMOylation 的潜在机制。我们首先通过抑制神经胶质瘤细胞线粒体自噬证明了 lncRNA RMST 的致癌活性。我们还首先确定 RMST 是 FUS SUMO 化的增强子，特别是增强 SUMO1 在 K333 处的修饰。 RMST 诱导的 SUMO 化有助于 FUS 和异质核核糖核蛋白 D (hnRNPD) 之间的相互作用，并稳定其表达和细胞线粒体自噬。重要的是，lncRNA RMST 可以作为神经胶质瘤患者的一个有希望的预后因素。我们的结果表明，lncRNA 的一种以前未知的功能可作为 FUS SUMOylation 的增强剂，而 RMST 将成为针对神经胶质瘤的药物开发的重要指导。
Long non-coding RNAs (lncRNAs) play a significant role in post-translational modifications of proteins, yet the importance of lncRNAs for SUMOylation is unknown. rhabdomyosarcoma 2 associated transcript (RMST) expression in glioma tissues and normal brain tissues was measured by quantitative real-time PCR and in situ hybridization. The functional roles of RMST in astrocytomas were demonstrated by a series of in vitro experiments. The potential mechanisms of RMST for SUMOylation were investigated by RNA immunoprecipitation, RNA pulldown, western blotting, and coimmunoprecipitation assays. We first demonstrated the oncogenic activity of lncRNA RMST by inhibiting glioma cells mitophagy. We also first determined that RMST is an enhancer of FUS SUMOylation, especially boosting SUMO1 modification at K333. SUMOylation induced by RMST contributes to the interaction between FUS and heterogeneous nuclear ribonucleoprotein D (hnRNPD) and stabilized their expression and cells mitophagy. Importantly, lncRNA RMST could serve as a promising prognostic factor for glioma patients. Our results demonstrated a previously unknown function of lncRNAs worked as an enhancer in FUS SUMOylation, and RMST will be a significant guide for the development of medications targeting gliomas.