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

Zhi-Wei Guo,Ying-Song Wu,Chen Xie,Xue-Xi Yang,Geng-Xi Cai,Xiang-Ming Zhai,Kun Li

doi:10.1093/database/baz027

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.

Highlights

Super-enhancers (SEs) are enriched with clustered mediator binding sites and a variety of chromatin signatures, such as H3K4me1, H3K4me3, H3K27ac and P300 acetyltransferase, which play essential roles in regulating gene expression [1,2,3]
For some long non-coding RNAs (lncRNAs) for which the function is known, we found that the pathological functions of 91 SE-lncRNAs were annotated by the LncRNADisease and Lnc2Cancer databases
To reveal the potential functions of TMPO-AS1-201 in these cancers, we investigated its significantly correlated genes in corresponding cancers and found that it was significantly correlated with thymopoietin (TMPO) in liver hepatocellular carcinoma (LIHC) and lung squamous cell carcinoma (LUSC) (Figure 3B), which indicated that TMPOAS1-201 may participate in tumorigenesis by regulating the gene expression of TMPO (Figure 3B)

Summary

Introduction

Super-enhancers (SEs) are enriched with clustered mediator binding sites and a variety of chromatin signatures, such as H3K4me, H3K4me, H3K27ac and P300 acetyltransferase, which play essential roles in regulating gene expression [1,2,3]. The enriched chromatin signature could reflect the regulatory roles of genomic regions; they could be applied to identify SEs [2]. SEs exist in a wide range of mammalian cells, and they can increase gene transcription over large genomic distances to regulate gene expression and to determine cell-type specificity [2, 4]. SEs have been shown to affect the invasion and metastasis of neuroendocrine tumor cells by controlling MET expression [7]. As SEs play important roles in controlling gene expression to regulate cellular physiological and pathological processes, it is necessary to reveal their underlying regulatory mechanisms

Methods

Results

Conclusion