LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations.
LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations.
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LncMAP：长非编码 RNA 介导的转录网络扰动的泛癌图谱
DOI：
10.1093/nar/gkx1311
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发表时间：
2018-02-16
影响因子：
14.9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Li Y;Li L;Wang Z;Pan T;Sahni N;Jin X;Wang G;Li J;Zheng X;Zhang Y;Xu J;Yi S;Li X
基因调控网络的扰动有助于癌症的发生和进展，然而，介导转录扰动的分子决定因素仍然是癌症生物学的一个基本挑战。我们发现转录干扰是由长链非编码rna （lncRNAs）通过整合全基因组转录调控与配对lncRNA和基因表达谱广泛介导的。系统构建泛癌LncRNA调制器图谱（LncRNA Modulator Atlas in Pan-cancer, lncrmap）发现，不同类型的LncRNA调节分子在多种组织中表达，表现出较高的保守性。引人注目的是，具有相似组织起源的癌症共享干扰细胞周期和免疫反应相关功能调节的lncRNA调节剂。此外，我们还发现了大量具有潜在临床意义的泛癌症lncRNA调节剂，这些调节剂在癌症中存在差异表达或与跨细胞系的药物敏感性密切相关。基于lncrna介导的转录扰动对癌症患者进行进一步分层，确定了具有不同存活率的亚型。最后，我们制作了一个用户友好的web界面，可用于探索跨癌症类型的lncrna介导的转录扰动。我们的研究为lncrna在癌症中介导的调控扰动提供了系统水平的解剖，也为研究lncrna在癌症中的功能提供了有价值的工具和资源。
Abstract Gene regulatory network perturbations contribute to the development and progression of cancer, however, molecular determinants that mediate transcriptional perturbations remain a fundamental challenge for cancer biology. We show that transcriptional perturbations are widely mediated by long noncoding RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with paired lncRNA and gene expression profiles. Systematic construction of an LncRNA Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA regulatory molecules, which are expressed in multiple tissues, exhibit higher conservation. Strikingly, cancers with similar tissue origin share lncRNA modulators which perturb the regulation of cell cycle and immune response-related functions. Furthermore, we identified a large number of pan-cancer lncRNA modulators with potential clinical significance, which are differentially expressed in cancer or are strongly correlated with drug sensitivity across cell lines. Further stratification of cancer patients based on lncRNA-mediated transcriptional perturbations identifies subtypes with distinct survival rates. Finally, we made a user-friendly web interface available for exploring lncRNA-mediated transcriptional perturbations across cancer types. Our study provides a systems-level dissection of lncRNA-mediated regulatory perturbations in cancer, and also presents a valuable tool and resource for investigating the function of lncRNAs in cancer.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
2
作者：
Knaack SA;Siahpirani AF;Roy S
通讯作者：
Roy S
识别和功能表征组织特异性和普遍表达的人类 lncRNA。
影响因子：
--
作者：
Jiang C;Li Y;Zhao Z;Lu J;Chen H;Ding N;Wang G;Xu J;Li X
通讯作者：
Li X
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ