Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades.

ABSTRACT: Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions. Due to their critical role, eRNAs are often dysregulated in cancer and growing number of interactions with chromatin modifiers, transcription factors, and splicing machinery have been described. Enhancer activation and eRNA transcription have particular relevance also in inflammatory response, placing the eRNAs at the interplay between cancer and immune cells. Here, we summarize all the possible molecular mechanisms recently reported in association with eRNAs activity.

SUBMITTER: Napoli S

PROVIDER: S-EPMC9030334 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades.

Napoli Sara S Munz Nicolas N Guidetti Francesca F Bertoni Francesco F

Cancers 20220414 8

Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short half-life but in some cases, once activated, they can be stably expressed and acquire additional functions. Due to their critical role, eRNAs are often d ...[more]

PMID: 35454885

Similar Datasets

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer.

Project description:Enzalutamide is a second-generation anti-androgen for treatment of castration-resistant prostate cancer (CPRC). It prolongs survival of CRPC patients, but its overall survival benefit is relatively modest (4.8 months) and by 24 months most patients progress on enzalutamide. To date, however, the molecular mechanisms underlying enzalutamide resistance remain elusive. Herein, we report enzalutamide treatment-induced alterations of androgen receptor (AR)-regulated enhancer RNAs (AR-eRNAs) and their roles in enzalutamide-resistant growth and survival of CRPC cells. AR chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) and RNA-seq analyses revealed that 188 and 227 AR-eRNAs were differentially expressed in enzalutamide-resistant LNCaP and C4-2 cells, respectively. The AR-eRNAs upregulated in C4-2 cells and downregulated in LNCaP cells were selected through meta-analysis. Expression of AR-eRNAs and related mRNAs in the loci of FTO, LUZP2, MARC1 and NCAM2 were further verified by real-time RT-PCR. Silencing of LUZP2 inhibited, but silencing of MARC1 increased the growth of enzalutamide-resistant C4-2 cells. Intriguingly, meta-analysis showed that expression of LUZP2 mRNA increased in primary tumors compared to normal prostate tissues, but decreased again in metastatic CRPC. Our findings suggest that eRNA alteration profiling is a viable new approach to identify functional gene loci that may not only contribute to enzalutamide-resistant growth of CRPC, but also serve as new targets for CRPC therapy.

| S-EPMC5122410 | biostudies-literature

eRNAs and super-enhancer lncRNAs are functional in human prostate cancer

Project description:Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. lncRNAs (long non-coding RNAs) play a significant role in the occurrence and development of PCa. eRNAs (enhancer RNA) and SE-lncRNAs (super-enhancer lncRNA) are important elements of lncRNAs, but the role of eRNAs and SE-lncRNAs in PCa remains largely unclear. In this work, we identified 681 eRNAs and 292 SE-lncRNAs that were expressed differentially in PCa using a microarray. We constructed a transcriptional regulation network that eRNA related enhancer and the target genes shared the same TF binding motifs. Further, we investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Our work provide a new perspective for developing medical treatments and therapies for prostate cancer.

2020-10-13 | GSE155056 | GEO

The emerging role of super enhancer-derived noncoding RNAs in human cancer.

Project description:Super enhancers (SEs) are large clusters of adjacent enhancers that drive the expression of genes which regulate cellular identity; SE regions can be enriched with a high density of transcription factors, co-factors, and enhancer-associated epigenetic modifications. Through enhanced activation of their target genes, SEs play an important role in various diseases and conditions, including cancer. Recent studies have shown that SEs not only activate the transcriptional expression of coding genes to directly regulate biological functions, but also drive the transcriptional expression of non-coding RNAs (ncRNAs) to indirectly regulate biological functions. SE-derived ncRNAs play critical roles in tumorigenesis, including malignant proliferation, metastasis, drug resistance, and inflammatory response. Moreover, the abnormal expression of SE-derived ncRNAs is closely related to the clinical and pathological characterization of tumors. In this review, we summarize the functions and roles of SE-derived ncRNAs in tumorigenesis and discuss their prospective applications in tumor therapy. A deeper understanding of the potential mechanism underlying the action of SE-derived ncRNAs in tumorigenesis may provide new strategies for the early diagnosis of tumors and targeted therapy.

| S-EPMC7532672 | biostudies-literature

eRNAs and Superenhancer lncRNAs Are Functional in Human Prostate Cancer.

Project description:Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. lncRNAs (long noncoding RNAs) play a significant role in the occurrence and development of PCa. eRNAs (enhancer RNAs) and SE-lncRNAs (superenhancer lncRNAs) are important elements of lncRNAs, but the role of eRNAs and SE-lncRNAs in PCa remains largely unclear. In this work, we identified 681 eRNAs and 292 SE-lncRNAs that were expressed differentially in PCa using a microarray. We also found that eRNAs transcribed from active open chromatin had significantly higher expression than those from active closed chromatin, and SE-lncRNAs had a little higher expression than eRNAs. Next, we constructed a transcriptional regulation network that eRNA-related enhancer and the target genes shared the same TF-binding motifs. Further, we investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Our work provides a new perspective for developing medical treatments and therapies for prostate cancer.

| S-EPMC7532396 | biostudies-literature

Prognostic Ability of Enhancer RNAs in Metastasis of Non-Small Cell Lung Cancer.

Project description:(1) Background: Non-small cell lung cancer (NSCLC) is the most common lung cancer. Enhancer RNA (eRNA) has potential utility in the diagnosis, prognosis and treatment of cancer, but the role of eRNAs in NSCLC metastasis is not clear; (2) Methods: Differentially expressed transcription factors (DETFs), enhancer RNAs (DEEs), and target genes (DETGs) between primary NSCLC and metastatic NSCLC were identified. Prognostic DEEs (PDEEs) were screened by Cox regression analyses and a predicting model for metastatic NSCLC was constructed. We identified DEE interactions with DETFs, DETGs, reverse phase protein arrays (RPPA) protein chips, immunocytes, and pathways to construct a regulation network using Pearson correlation. Finally, the mechanisms and clinical significance were explained using multi-dimensional validation unambiguously; (3) Results: A total of 255 DEEs were identified, and 24 PDEEs were selected into the multivariate Cox regression model (AUC = 0.699). Additionally, the NSCLC metastasis-specific regulation network was constructed, and six key PDEEs were defined (ANXA8L1, CASTOR2, CYP4B1, GTF2H2C, PSMF1 and TNS4); (4) Conclusions: This study focused on the exploration of the prognostic value of eRNAs in the metastasis of NSCLC. Finally, six eRNAs were identified as potential markers for the prediction of metastasis of NSCLC.

| S-EPMC9268450 | biostudies-literature

A genome-wide CRISPR activation screen identifies <i>SCREEM</i> a novel <i>SNAI1</i> super-enhancer demarcated by eRNAs.

Project description:The genome is pervasively transcribed to produce a vast array of non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides and are best known for their ability to regulate gene expression. Enhancer RNAs (eRNAs) are subclass of lncRNAs that are synthesized from enhancer regions and have also been shown to coordinate gene expression. The biological function and significance of most lncRNAs and eRNAs remain to be determined. Epithelial to mesenchymal transition (EMT) is a ubiquitous cellular process that occurs during cellular migration, homeostasis, fibrosis, and cancer-cell metastasis. EMT-transcription factors, such as SNAI1 induce a complex transcriptional program that coordinates the morphological and molecular changes associated with EMT. Such complex transcriptional programs are often subject to coordination by networks of ncRNAs and thus can be leveraged to identify novel functional ncRNA loci. Here, using a genome-wide CRISPR activation (CRISPRa) screen targeting ∼10,000 lncRNA loci we identified ncRNA loci that could either promote or attenuate EMT. We discovered a novel locus that we named SCREEM (SNAI1 cis-regulatory eRNAs expressed in monocytes). The SCREEM locus contained a cluster of eRNAs that when activated using CRISPRa induced expression of the neighboring gene SNAI1, driving concomitant EMT. However, the SCREEM eRNA transcripts themselves appeared dispensable for the induction of SNAI1 expression. Interestingly, the SCREEM eRNAs and SNAI1 were co-expressed in activated monocytes, where the SCREEM locus demarcated a monocyte-specific super-enhancer. These findings suggest a potential role for SNAI1 in monocytes. Exploration of the SCREEM-SNAI axis could reveal novel aspects of monocyte biology.

| S-EPMC10009272 | biostudies-literature

Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems.

Project description:Genomic enhancer elements regulate gene expression programs important for neuronal fate and function and are implicated in brain disease states. Enhancers undergo bidirectional transcription to generate non-coding enhancer RNAs (eRNAs). However, eRNA function remains controversial. Here, we combined Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq) and RNA-Seq datasets from three distinct neuronal culture systems in two activity states, enabling genome-wide enhancer identification and prediction of putative enhancer-gene pairs based on correlation of transcriptional output. Notably, stimulus-dependent enhancer transcription preceded mRNA induction, and CRISPR-based activation of eRNA synthesis increased mRNA at paired genes, functionally validating enhancer-gene predictions. Focusing on enhancers surrounding the Fos gene, we report that targeted eRNA manipulation bidirectionally modulates Fos mRNA, and that Fos eRNAs directly interact with the histone acetyltransferase domain of the enhancer-linked transcriptional co-activator CREB-binding protein (CBP). Together, these results highlight the unique role of eRNAs in neuronal gene regulation and demonstrate that eRNAs can be used to identify putative target genes.

| S-EPMC7515708 | biostudies-literature

Integrator mediates the biogenesis of enhancer RNAs.

Project description:Integrator is a multi-subunit complex stably associated with the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII). Integrator is endowed with a core catalytic RNA endonuclease activity, which is required for the 3'-end processing of non-polyadenylated, RNAPII-dependent, uridylate-rich, small nuclear RNA genes. Here we examine the requirement of Integrator in the biogenesis of transcripts derived from distal regulatory elements (enhancers) involved in tissue- and temporal-specific regulation of gene expression in metazoans. Integrator is recruited to enhancers and super-enhancers in a stimulus-dependent manner. Functional depletion of Integrator subunits diminishes the signal-dependent induction of enhancer RNAs (eRNAs) and abrogates stimulus-induced enhancer-promoter chromatin looping. Global nuclear run-on and RNAPII profiling reveals a role for Integrator in 3'-end cleavage of eRNA primary transcripts leading to transcriptional termination. In the absence of Integrator, eRNAs remain bound to RNAPII and their primary transcripts accumulate. Notably, the induction of eRNAs and gene expression responsiveness requires the catalytic activity of Integrator complex. We propose a role for Integrator in biogenesis of eRNAs and enhancer function in metazoans.

| S-EPMC4718573 | biostudies-literature

Enhancer RNA transcriptomics-wide association study reveals an atlas of pan-cancer susceptibility eRNAs

Project description:Increasing evidence has demonstrated that enhancer RNAs (eRNAs) play essential roles in human diseases. However, the complete identification of disease-related subsets of eRNAs remains a major challenge. Here, we construct an atlas of common and rare genetic variants influencing the expression of enhancer RNAs across 49 human tissues. We identify 11,757 eRNA quantitative trait loci (eRNA-QTLs) associated with the expression of 89.75% annotated eRNAs. Mechanically, eRNA-QTLs frequently altered the binding motifs of transcription factors and were further experimentally validated by CRISPR-based base editing. We also observed that 28.48% of cancer signals were co-localized with eRNA-QTLs. Utilizing our newly developed eRNA transcriptome-wide association study (eRNA-TWAS) model, we have effectively identified 259 cancer susceptibility eRNAs spanning 23 distinct cancer types. Notably, among the identified eRNAs, these eRNA-linked cancer susceptibility genes exhibit significant dependence across various cancer cell lines. Interestingly, cancer risk can be significantly influenced by rare functional variants that are linked to eRNAs with transcriptomic outliers. Additionally, we develop a comprehensive and flexible data portal for exploring the genetic underpinnings of eRNAs. Overall, this study reveals a systematic landscape of genetic dependencies on eRNAs across pan-cancers and significantly expands the pool of disease-associated eRNAs.

2025-02-13 | GSE242322 | GEO

Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer.

Project description:Enhancer RNA (eRNA) is a type of noncoding RNA transcribed from the enhancer. Although critical roles of eRNA in gene transcription control have been increasingly realized, the systemic landscape and potential function of eRNAs in cancer remains largely unexplored. Here, we report the integration of multi-omics and pharmacogenomics data across large-scale patient samples and cancer cell lines. We observe a cancer-/lineage-specificity of eRNAs, which may be largely driven by tissue-specific TFs. eRNAs are involved in multiple cancer signaling pathways through putatively regulating their target genes, including clinically actionable genes and immune checkpoints. They may also affect drug response by within-pathway or cross-pathway means. We characterize the oncogenic potential and therapeutic liability of one eRNA, NET1e, supporting the clinical feasibility of eRNA-targeted therapy. We identify a panel of clinically relevant eRNAs and developed a user-friendly data portal. Our study reveals the transcriptional landscape and clinical utility of eRNAs in cancer.

| S-EPMC6783481 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data