Roles of circular RNA in cardiac fibrosis
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PROVIDER: PRJNA1003391 | ENA |
REPOSITORIES: ENA
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Project description:Heart failure is one of the leading causes of death and it often accompanies activation of quiescent cardiac myofibroblasts, which results in cardiac fibrosis and resulting cardiac remodeling. Circular RNA, one form of non-coding RNA discovered recently, is formed by backsplicing of 3’ end to 5’ end of exons and is known to be closely related to the variety of pathophysiological function as well as normal homeostasis. However, its roles in the cardiovascular diseases, especially in cardiac fibrosis, are not fully studied. Circular RNAs (circRNAs) are formed by backsplicing events of 3′ end to 5′ end. To identify circRNA candidates, RNA sequencing (RNA-seq) datasets were obtained from transverse aortic constriction (TAC)-induced hearts. Especially, we were interested in cardiac fibroblast-specific circRNAs that affect its differentiation and cardiac fibrosis. Thus, in the present study, by utilizing RNA sequencing analysis followed by diverse bioinformatic or biochemical studies, we identified and characterized circRNA that may affect the pathologic remodeling of heart.
2023-12-14 | GSE240332 | GEO
Project description:Translational control of cardiac fibrosis
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Project description:Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides the evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.
2023-07-04 | GSE236454 | GEO
Project description:The pervasive expression of circular RNA from protein coding loci is a recently discovered feature of many eukaryotic gene expression programs. Computational methods to discover and quantify circular RNA are essential to the study of the mechanisms of circular RNA biogenesis and potential functional roles they may play. In this paper, we present a new statistical algorithm that increases the sensitivity and specificity of circular RNA detection.by discovering and quantifying circular and linear RNA splicing events at both annotated exon boundaries and in un-annotated regions of the genome Unlike previous approaches which rely on heuristics like read count and homology between exons predicted to be circularized to determine confidence in prediction of circular RNA expression, our algorithm is a statistical approach. We have used this algorithm to discover general induction of circular RNAs in many tissues during human fetal development. We find that some regions of the brain show marked enrichment for genes where circular RNA is the dominant isoform. Beyond this global trend, specific circular RNAs are tissue specifically induced during fetal development, including a circular isoform of NCX1 in the developing fetal heart that, by 20 weeks, is more highly expressed than the linear isoform as well as beta-actin. In addition, while the vast majority of circular RNA production occurs at canonical U2 (major spliceosome) splice sites, we find the first examples of developmentally induced circular RNAs processed by the U12 (minor) spliceosome, and an enriched propensity of U12 donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, our algorithm and its results suggest a potentially significant role for circular RNA in human development. 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kit.
2015-06-25 | E-GEOD-64283 | biostudies-arrayexpress
Project description:We discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.
2015-06-25 | E-GEOD-64417 | biostudies-arrayexpress
Project description:Genome-wide circular RNA profiling analyses in left ventricles (LVs) from cardiac-specific GRK-beta1AR transgenic (TG) and/or miR-150 TG mice treated with isoproterenol (ISO) were performed to identify novel circular RNAs regulated by beta-arrestin-mediated beta1AR signaling and miR-150 in the heart.
2023-01-01 | GSE199290 | GEO
Project description:Translational control of cardiac fibrosis (I)
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Project description:Translational control of cardiac fibrosis (II)
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Project description:Deletion of Tmem43 encoding nuclear membrane protein TMEM43, specifically in mouse cardiac myocytes leads to cardiac fibrosis and dysfunction. Temporal RNA-seq identified early and late trascriptomic changes and implicates TGFb1 in the pathogenesis of ACM caused by Tmem43 haploinsufficiency.
2021-02-26 | GSE147317 | GEO
Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and disease remains obscure. Here, we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease.
2017-03-28 | MSV000080698 | MassIVE