CTCF公司
增强子
染色质
生物
减压
粘蛋白
胶质瘤
抑制因子
肿瘤转化
基因敲除
遗传学
细胞生物学
作者
Evgeny Deforzh,Erik J Uhlmann,Eashita Das,Aleksandra Galitsyna,Ramil Arora,Harini Saravanan,Rosalia Rabinovsky,Aditya D Wirawan,Nadiya M Teplyuk,Rachid El Fatimy,Sucika Perumalla,Anirudh Jairam,Zhiyun Wei,Leonid Mirny,Anna M Krichevsky
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-04-01
卷期号:82 (10): 1894-1908.e5
被引量:3
标识
DOI:10.1016/j.molcel.2022.03.018
摘要
miR-10b is silenced in normal neuroglial cells of the brain but commonly activated in glioma, where it assumes an essential tumor-promoting role. We demonstrate that the entire miR-10b-hosting HOXD locus is activated in glioma via the cis-acting mechanism involving 3D chromatin reorganization and CTCF-cohesin-mediated looping. This mechanism requires two interacting lncRNAs, HOXD-AS2 and LINC01116, one associated with HOXD3/HOXD4/miR-10b promoter and another with the remote enhancer. Knockdown of either lncRNA in glioma cells alters CTCF and cohesin binding, abolishes chromatin looping, inhibits the expression of all genes within HOXD locus, and leads to glioma cell death. Conversely, in cortical astrocytes, enhancer activation is sufficient for HOXD/miR-10b locus reorganization, gene derepression, and neoplastic cell transformation. LINC01116 RNA is essential for this process. Our results demonstrate the interplay of two lncRNAs in the chromatin folding and concordant regulation of miR-10b and multiple HOXD genes normally silenced in astrocytes and triggering the neoplastic glial transformation.
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