Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3.
Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3.
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胶质母细胞瘤词干样细胞中印迹DLK1-DIO3区域的放松调节表达：lncRNA MEG3的肿瘤抑制作用。
DOI：
10.1093/neuonc/noaa127
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发表时间：
2020-12-18
期刊：
影响因子：
15.9
通讯作者：
Ricci-Vitiani L
中科院分区：
文献类型：
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作者：
Buccarelli M;Lulli V;Giuliani A;Signore M;Martini M;D'Alessandris QG;Giannetti S;Novelli A;Ilari R;Giurato G;Boe A;Castellani G;Spartano S;Marangi G;Biffoni M;Genuardi M;Pallini R;Marziali G;Ricci-Vitiani L
胶质母细胞瘤（GBM）干细胞样细胞（GSC）被认为负责GBM的维持和侵袭性，GBM是成人中最常见的原发性脑肿瘤。本研究旨在阐明GBM发病机制中染色体14 q32上的印迹δ样同源物1基因Ⅲ型碘甲状腺原氨酸脱碘酶基因（DLK-DIO 3）区域内的失调。对GSC和GBM组织进行实时PCR分析。甲基化分析，基因表达，和反相蛋白质阵列配置文件被用来调查的母亲表达3基因（MEG 3）的肿瘤抑制功能。与正常脑组织相比，在GSC和GBM组织中观察到DLK 1-DIO 3区域内的基因和非编码RNA表达缺失。这种下调主要由表观遗传沉默介导。Kaplan-Meier分析表明，MEG 3和MEG 8长非编码（lnc）RNA的低表达与GBM患者的短生存期显著相关。MEG 3恢复通过抑制细胞生长、迁移和集落形成来损害体外GSC的致瘤能力，并减少体内肿瘤生长，减少浸润性生长。这些作用与调节细胞粘附和上皮-间充质转化（EMT）相关的基因有关。在GBM中，MEG 3作为肿瘤抑制因子，主要调节细胞粘附、EMT和细胞增殖，从而为新型GBM疗法提供了潜在的候选药物。
Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene‒type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan–Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies.
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影响因子：
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Long J;Pi X
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Pi X
影响因子：
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