Enhancer RNAs: Insights Into Their Biological Role

Lara, Josué Cortés-Fernández de; Arzate-Mejía, Rodrigo G.; Recillas‐Targa, Félix

doi:10.1177/2516865719846093

Cited by 23 publications

(14 citation statements)

References 60 publications

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“…Currently estimated at more than 56,000 [144], the number of lncRNA genes more than doubles the number of protein‐coding genes in the human genome, although due their low expression levels, many lncRNAs remain poorly characterized and annotated [145], so that it is likely that this number will be increased in the years to come. Based on their presumed function lncRNAs have been classified in a number of functional groups: competitive endogenous lncRNAs (ceRNAs) and circular lncRNAs (circRNAs), with potential roles as miRNA inhibitors [146,147], enhancer‐related RNAs (eRNAs), involved in transcriptional regulation [148], transcribed ultraconserved RNAs (T‐UCRs), transcribed from non‐coding highly conserved genomic regions [149], and the highly heterogeneous natural antisense transcripts (NATs), intronic lncRNAS and long intergenic RNAs (lincRNAs) among others, although this classification is neither exhaustive (see [150] for a recent and comprehensive review on the topic) nor unambiguous since a lncRNA could easily fit into more than one group [151].…”

Section: Long Non‐coding Rnas (Lncrnas) and Their Functional Relationmentioning

confidence: 99%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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Completion of the human genome sequencing project highlighted the richness of the cellular RNA world, and opened the door to the discovery of a plethora of short and long non‐coding RNAs (the dark transcriptome) with regulatory or structural potential, which shifted the balance of pathological gene alterations from coding to non‐coding RNAs. Thus, disease risk assessment currently has to also evaluate the expression of new RNAs such as small micro RNAs (miRNAs), long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs), competing endogenous RNAs (ceRNAs), retrogressed elements, 3′UTRs of mRNAs, etc. We are interested in the pathogenic mechanisms of atherosclerosis (ATH) progression in patients suffering Chronic Kidney Disease, and in this review, we will focus in the role of the dark transcriptome (non‐coding RNAs) in ATH progression. We will focus in miRNAs and in the formation of regulatory axes or networks with their mRNA targets and with the lncRNAs that function as miRNA sponges or competitive inhibitors of miRNA activity. In this sense, we will pay special attention to retrogressed genomic elements, such as processed pseudogenes and Alu repeated elements, that have been recently seen to also function as miRNA sponges, as well as to the use or miRNA derivatives in gene silencing, anti‐ATH therapies. Along the review, we will discuss technical developments associated to research in lncRNAs, from sequencing technologies to databases, repositories and algorithms to predict miRNA targets, as well as new approaches to miRNA function, such as integrative or enrichment analysis and their potential to unveil RNA regulatory networks.

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Section: Long Non‐coding Rnas (Lncrnas) and Their Functional Relationmentioning

confidence: 99%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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“…LncRNAs do not have protein translation capabilities, but they play an important role in various processes by directly or indirectly regulating protein expression [12]. LncRNAs can not only directly participate in the regulation of gene expression but can also act as competing endogenous RNAs (ceRNAs) to interact with miRNAs [13, 14]. A microRNA (miRNA) is an evolutionarily conserved single-stranded RNA that typically contains 21–24 nucleotides [15].…”

Section: Introductionmentioning

confidence: 99%

LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis

et al. 2019

Aging

113

100

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Aim: To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 (MBTD1) axis.Results: The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.Conclusion: In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.Methods: The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.

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“…The transcriptional activity at the active enhancers results in the production of enhancer RNAs (eRNAs), which may regulate their target gene by altering the chromatin architecture and histone modification, or by recruiting specific proteins to the enhancers ( 56 ). Super-enhancers are reported to produce higher amounts of eRNAs than typical enhancers ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells

et al. 2021

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The proprotein convertase enzyme FURIN promotes the proteolytic maturation of pro-proteins and thereby it serves as an important factor for maintaining cellular homeostasis. In T cells, FURIN is critical for maintaining the T regulatory cell dependent peripheral immune tolerance and intact T helper cell polarization. The enzymatic activity of FURIN is directly associated with its expression levels, but genetic determinants for cell-type specific Furin gene regulation have remained elusive. By exploring the histone acetyltransferase p300 binding patterns in T helper cells, a putative regulatory region at ca. 20kB upstream of Furin gene was identified. When this region was deleted with CRISPR/Cas9 the production of Furin mRNA was significantly reduced in activated mouse T cells. Genome-wide RNA profiling by sequencing revealed that the novel Furin regulator region also impacted the expression of several genes that have previously been associated with the Th1 type hall mark cytokine IFNγ regulation or function. Finally, Furin genetic regulatory region was found to specifically promote the secretion of IFNγ by activated T cells. In sum, our data unravels the presence of Furin expression regulatory region in T cells that has characteristics of a super-enhancer for Th1 cell fate.

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Enhancer RNAs: Insights Into Their Biological Role

Cited by 23 publications

References 60 publications

Unveiling ncRNA regulatory axes in atherosclerosis progression

Unveiling ncRNA regulatory axes in atherosclerosis progression

LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis

Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells

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