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LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations

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 noncodin...

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Detalles Bibliográficos
Autores principales: Li, Yongsheng, Li, Lili, Wang, Zishan, Pan, Tao, Sahni, Nidhi, Jin, Xiyun, Wang, Guangjuan, Li, Junyi, Zheng, Xiangyi, Zhang, Yunpeng, Xu, Juan, Yi, Song, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815097/
https://www.ncbi.nlm.nih.gov/pubmed/29325141
http://dx.doi.org/10.1093/nar/gkx1311
Descripción
Sumario: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.