Dataset Information

SELER: a database of super-enhancer-associated lncRNA- directed transcriptional regulation in human cancers.

ABSTRACT: Super-enhancers (SEs) are enriched with a cluster of mediator binding sites, which are major contributors to cell-type-specific gene expression. Currently, a large quantity of long non-coding RNAs has been found to be transcribed from or to interact with SEs, which constitute super-enhancer associated long non-coding RNAs (SE-lncRNAs). These SE-lncRNAs play essential roles in transcriptional regulation through controlling SEs activity to regulate a broad range of physiological and pathological processes, especially tumorigenesis. However, the pathological functions of SE-lncRNAs in tumorigenesis are still obscure. In this paper, we characterized 5056 SE-lncRNAs and their associated genes by analysing 102 SE data sets. Then, we analysed their expression profiles and prognostic information derived from 19 cancer types to identify cancer-related SE-lncRNAs and to explore their potential functions. In total, 436 significantly differentially expressed SE-lncRNAs and 2035 SE-lncRNAs with high prognostic values were identified. Additionally, 3935 significant correlations between SE-lncRNAs and their regulatory genes were further validated by calculating their correlation coefficients in each cancer type. Finally, the SELER database incorporating the aforementioned data was provided for users to explore their physiological and pathological functions to comprehensively understand the blocks of living systems.

SUBMITTER: Guo ZW

PROVIDER: S-EPMC6390648 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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SELER: a database of super-enhancer-associated lncRNA- directed transcriptional regulation in human cancers.

Guo Zhi-Wei ZW Xie Chen C Li Kun K Zhai Xiang-Ming XM Cai Geng-Xi GX Yang Xue-Xi XX Wu Ying-Song YS

Database : the journal of biological databases and curation 20190101

Super-enhancers (SEs) are enriched with a cluster of mediator binding sites, which are major contributors to cell-type-specific gene expression. Currently, a large quantity of long non-coding RNAs has been found to be transcribed from or to interact with SEs, which constitute super-enhancer associated long non-coding RNAs (SE-lncRNAs). These SE-lncRNAs play essential roles in transcriptional regulation through controlling SEs activity to regulate a broad range of physiological and pathological p ...[more]

PMID: 30806704

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Project description:BackgroundSuper-enhancers (SEs), driving high-level expression of genes with tumor-promoting functions, have been investigated recently. However, the roles of super-enhancer-associated lncRNAs (SE-lncRNAs) in tumors remain undetermined, especially in gliomas. We here established a SE-lncRNAs expression-based prognostic signature to choose the effective treatment of glioma and identify a novel therapeutic target.MethodsCombined analysis of RNA sequencing (RNA-seq) data and ChIP sequencing (ChIP-seq) data of glioma patient-derived glioma stem cells (GSCs) screened SE-lncRNAs. Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets served to construct and validate SE-lncRNA prognostic signature. The immune profiles and potential immuno- and chemotherapies response prediction value of the signature were also explored. Moreover, we verified the epigenetic activation mechanism of LINC00945 via the ChIP assay, and its effect on glioma was determined by performing the functional assay and a mouse xenograft model.Results6 SE-lncRNAs were obtained and identified three subgroups of glioma patients with different prognostic and clinical features. A risk signature was further constructed and demonstrated to be an independent prognostic factor. The high-risk group exhibited an immunosuppressive microenvironment and was higher enrichment of M2 macrophage, regulatory T cells (Tregs), and Cancer-associated fibroblasts (CAFs). Patients in the high-risk group were better candidates for immunotherapy and chemotherapeutics. The SE of LINC00945 was further verified via ChIP assay. Mechanistically, BRD4 may mediate epigenetic activation of LINC00945. Additionally, overexpression of LINC00945 promoted glioma cell proliferation, EMT, migration, and invasion in vitro and xenograft tumor formation in vivo.ConclusionOur study constructed the first prognostic SE-lncRNA signature with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.

Dataset Information

SELER: a database of super-enhancer-associated lncRNA- directed transcriptional regulation in human cancers.

Publications

SELER: a database of super-enhancer-associated lncRNA- directed transcriptional regulation in human cancers.

Similar Datasets

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