Large-scale sequencing studies discovered substantial genetic variants occurring in enhancers which regulate genes via long range chromatin interactions. Importantly, such variants could affect enhancer regulation by changing transcription factor bindings or enhancer hijacking, and in turn, make an essential contribution to disease progression. To facilitate better usage of published data and exploring enhancer deregulation in various human diseases, we created DiseaseEnhancer (http://biocc.hrbmu.edu.cn/DiseaseEnhancer/), a manually curated database for disease-associated enhancers. As of July 2017, DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases. Database features include basic enhancer information (i.e. genomic location and target genes); disease types; associated variants on the enhancer and their mediated phenotypes (i.e. gain/loss of enhancer and the alterations of transcription factor bindings). We also include a feature on our website to export any query results into a file and download the full database. DiseaseEnhancer provides a promising avenue for researchers to facilitate the understanding of enhancer deregulation in disease pathogenesis, and identify new biomarkers for disease diagnosis and therapy.
Edited by Joel M. GottesfeldOver the past decade, thousands of long noncoding RNAs (lncRNAs) have been identified, many of which play crucial roles in normal physiology and human disease. LncRNAs can interact with chromatin and then recruit protein complexes to remodel chromatin states, thus regulating gene expression. However, how lncRNA-chromatin interactions contribute to their biological functions is largely unknown. Here, we collected and constructed an atlas of 188,647 lncRNA-chromatin interactions in human and mouse. All lncRNAs showed diverse epigenetic modification patterns at their binding sites, especially the marks of enhancer activity. Functional analysis of lncRNA target genes further revealed that lncRNAs could exert their functions by binding to both promoter and distal regulatory elements, especially the distal regulatory elements. Intriguingly, many important pathways were observed to be widely regulated by lncRNAs through distal binding. For example, NEAT1, a cancer lncRNA, controls 13.3% of genes in the PI3K-AKT signaling pathway by interacting with distal regulatory elements. In addition, "twogene" signatures composed of a lncRNA and its distal target genes, such as HOTAIR-CRIM1, provided significant clinical benefits relative to the lncRNA alone. In summary, our findings underscored that lncRNA-distal interactions were essential for lncRNA functions, which would provide new clues to understand the molecular mechanisms of lncRNAs in complex disease.
Despite highly successful treatments for localized prostate cancer (PCa), prognostic biomarkers are needed to improve patient management and prognosis. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are key regulators with biological and clinical significance. By transcriptome analysis, we identified a set of consistently dysregulated lncRNAs in PCa across different datasets and revealed an eight-lncRNA signature that significantly associated with the biochemical recurrence (BCR)-free survival. Based on the signature, patients could be classified into high- and low-risk groups with significantly different survival (HR = 2.19; 95% CI = 1.67–2.88; P < 0.0001). Validations in the validation cohorts and another independent cohort confirmed its prognostic value for recurrence prediction. Multivariable analysis showed that the signature was independent of common clinicopathological features and stratified analysis further revealed its role in elevating risk stratification of current prognostic models. Additionally, the eight-lncRNA signature was able to improve on the CAPRA-S score for the prediction of BCR as well as to reflect the metastatic potential of PCa. Functional characterization suggested that these lncRNAs which showed PCa-specific expression patterns may involve in critical processes in tumorigenesis. Overall, our results demonstrated potential application of lncRNAs as novel independent biomarkers. The eight-lncRNA signature may have clinical potential for facilitating further stratification of more aggressive patients who would benefit from adjuvant therapy.
DGs are the most common primary malignant brain tumours in adults, with an age-adjusted mortality rate of 4.25/100,000 per year in the United States [1]. To understand gliomagenesis, molecular changes in large cohorts of DGs have been described previously [2,3]. These large-scale studies established the full spectrum of genomic alterations and revealed extensive molecular heterogeneity among individuals. Recent genomic studies have documented that individual cancer samples display genetic heterogeneity and contain subclonal populations [4]. The presence of multiple clones within a single tumour has been explained as a Darwinian evolutionary
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