LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis.
LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis.
复制标题
LNCRNA linc00998通过CBX3介导的C-MET/AKT/MTOR轴抑制恶性神经胶质瘤表型。
DOI：
10.1038/s41419-020-03247-6
复制
发表时间：
2020-12-02
影响因子：
9
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Cai H;Yu Y;Ni X;Li C;Hu Y;Wang J;Chen F;Xi S;Chen Z
长链非编码RNA（lncRNA），曾经被认为是进化的无功能遗物，正在成为肿瘤进展中的必需基因。然而，lncRNA在胶质瘤中的功能和潜在机制尚不清楚。本研究旨在研究LINC 00998在胶质瘤进展中的作用。通过TCGA数据库的筛选，我们发现LINC 00998在胶质母细胞瘤组织中下调，并且LINC 00998的低表达与不良预后相关。过表达LINC 00998可抑制胶质瘤细胞的增殖，阻断G1/S细胞周期转换，从而抑制胶质瘤的进展。从机制上讲，RNA下拉和质谱分析结果显示LINC 00998和CBX 3之间存在相互作用。IP实验证明LINC 00998可以稳定CBX 3并阻止其泛素化降解。GSEA表明LINC 00998可以调节c-Met/Akt/mTOR信号通路，这通过使用siRNA介导的CBX 3和Akt抑制剂MK 2206的敲低的拯救测定进一步证实。此外，双荧光素酶分析显示miR-34 c-5 p可直接与LINC 00998结合并下调其表达。我们的研究结果表明LINC 00998是一种新的胶质瘤肿瘤抑制因子，LINC 00998可能是一种新的预后生物标志物，为胶质瘤患者的精确治疗提供了策略。
Long noncoding RNAs (lncRNAs), once considered to be nonfunctional relics of evolution, are emerging as essential genes in tumor progression. However, the function and underlying mechanisms of lncRNAs in glioma remain unclear. This study aimed to investigate the role of LINC00998 in glioma progression. Through screening using TCGA database, we found that LINC00998 was downregulated in glioblastoma tissues and that low expression of LINC00998 was associated with poor prognosis. Overexpression of LINC00998 inhibited glioma cell proliferation in vitro and in vivo and blocked the G1/S cell cycle transition, which exerted a tumor-suppressive effect on glioma progression. Mechanistically, RNA pull-down and mass spectrometry results showed an interaction between LINC00998 and CBX3. IP assays demonstrated that LINC00998 could stabilize CBX3 and prevent its ubiquitination degradation. GSEA indicated that LINC00998 could regulate the c-Met/Akt/mTOR signaling pathway, which was further confirmed by a rescue assay using siRNA-mediated knockdown of CBX3 and the Akt inhibitor MK2206. In addition, dual-luciferase assays showed that miR-34c-5p could directly bind to LINC00998 and downregulate its expression. Our results identified LINC00998 as a novel tumor suppressor in glioma, and LINC00998 could be a novel prognostic biomarker, providing a strategy for precision therapy in glioma patients.
登录
查看更多内容
Diana-LNCBASE：长期非编码RNA上经过实验验证和计算预测的microRNA靶标。
影响因子：
14.9
作者：
Paraskevopoulou MD;Georgakilas G;Kostoulas N;Reczko M;Maragkakis M;Dalamagas TM;Hatzigeorgiou AG
通讯作者：
Hatzigeorgiou AG
影响因子：
3.5
作者：
Koike, N;Maita, H;Iguchi-Ariga, SMM
通讯作者：
Iguchi-Ariga, SMM
缺氧诱导的 lncRNA PDIA3P1 通过 miR-124-3p 海绵作用促进胶质瘤中的间质转化
影响因子：
9
作者：
Wang, Shaobo;Qi, Yanhua;Li, Gang
通讯作者：
Li, Gang
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
64.8
作者：
Lachner, M;O'Carroll, N;Jenuwein, T
通讯作者：
Jenuwein, T