Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 25, 2022

Abstract Epigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses candidate gene approaches illustrate the multigenic complexity of disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, noncoding RNA, which are importance for disease development regression. Targeting key enzymes, especially methyltransferases, acetylases, deacetylases their regulated target genes, could represent an attractive new route diagnosis treatment Herein, we summarize knowledge on history essential regulatory mechanisms in Furthermore, discuss preclinical studies drugs that targeted these enzymes diseases therapy. Finally, conclude clinical trials going some processes.

Language: Английский

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LncRNA MIAT sponges miR-149-5p to inhibit efferocytosis in advanced atherosclerosis through CD47 upregulation

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(2)

Published: Feb. 12, 2019

Atherosclerotic cardio-cerebrovascular disease and death remain the leading cause of morbidity mortality worldwide. Defective efferocytosis, clearance apoptotic cells by macrophages, is thought to lead increased inflammation necrotic core formation in atherosclerotic lesions. However, very little known about role long noncoding RNA (lncRNA) during this process. Here we show that lncRNA myocardial infarction associated transcript (MIAT) was markedly elevated serum patients with symptoms vulnerable plaque macrophages cores an advanced atherosclerosis mouse model. MIAT knockdown attenuated progression, reduced size, stability vivo. Furthermore, promoted vivo vitro. Mechanistic studies revealed acted as a micro (miRNA) sponge positively modulate expression anti-phagocytic molecule CD47 through sponging miR-149-5p. Together, these findings identified macrophage MIAT/miR-149-5p /CD47 pathway key factor development plaques.

Language: Английский

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Circular RNAs: Expression, localization, and therapeutic potentials

Molecular Therapy, Journal Year: 2021, Volume and Issue: 29(5), P. 1683 - 1702

Published: Jan. 21, 2021

Circular RNAs (circRNAs) are with a unique circular structure that is generated from back-splicing processes. These molecules were discovered more than 40 years ago but failed to raise scientific interest until lately. Increasing studies have found these might not just be byproducts of the splicing process possess important regulatory functions through different cellular events. Most currently being studied in field cancer, and many them been confirmed involved tumorigenesis. However, implicated developmental stages diseases other cancer. In this review, we focus on discussing role non-cancer diseases, especially cardiovascular diseases. Following summary life cycle circRNAs, provide input studying circRNA-protein interactions based our experience, which modulate protein translocation. Furthermore, outline potential circRNAs potent biomarkers, effective therapeutic targets, treatments as well fields. Viroids first pathogens. Sanger et al.1Sanger H.L. Klotz G. Riesner D. Gross H.J. Kleinschmidt A.K. single-stranded covalently closed RNA existing highly base-paired rod-like structures.Proc. Natl. Acad. Sci. USA. 1976; 73: 3852-3856Crossref PubMed Scopus (1057) Google Scholar described viroids 1976 "single-stranded molecules." this, another study conducted by Hsu Coca-Prados2Hsu M.T. Coca-Prados M. Electron microscopic evidence for form cytoplasm eukaryotic cells.Nature. 1979; 280: 339-340Crossref (463) 1979 some no free flanking ends. They raised possibility circularity dependent any interactions. During period time, follow up unexpected findings due an explosion linear RNA, after polymerase chain reaction was invented 1985. There late 1990s transcript products non-canonical splicing. reported deletion colon cancer gene3Nigro J.M. Cho K.R. Fearon E.R. Kern S.E. Ruppert Oliner J.D. Kinzler K.W. Vogelstein B. Scrambled exons.Cell. 1991; 64: 607-613Abstract Full Text PDF (616) human EST-1 gene,4Cocquerelle C. Daubersies P. Majérus M.A. Kerckaert J.P. Bailleul Splicing inverted order exons occurs proximal large introns.EMBO J. 1992; 11: 1095-1098Crossref their isoforms. Later, few proposed biogenesis mechanisms molecules. A well-known hypothesis Dubin al.5Dubin R.A. Kazmi Ostrer H. Inverted repeats necessary circularization mouse testis Sry transcript.Gene. 1995; 167: 245-248Crossref (99) circRNA sry complementary intronic sequences drive circularization. Another Pasman al.6Pasman Z. Been M.D. Garcia-Blanco Exon mammalian nuclear extracts.RNA. 1996; 2: 603-610PubMed could produced extracts. mostly located expressed stage tissue-specific manner. Up beginning 21st century, number increased, they still sporadic. People classified non-linear mRNAs,7Dixon R.J. Eperon I.C. Hall L. Samani N.J. genome-wide survey demonstrates widespread mRNA multiple species.Nucleic Acids Res. 2005; 33: 5904-5913Crossref (30) scrambled exons, or exon shuffling.8Al-Balool H.H. Weber Liu Y. Wade Guleria K. Nam P.L. Clayton Rowe W. Coxhead Irving al.Post-transcriptional shuffling events humans can evolutionarily conserved abundant.Genome 2011; 21: 1788-1799Crossref (34) generally regarded errors rare held little significance. Although presence documented decades ago, very about understood past decade. Starting 2010, advancements RNA-sequencing technologies along buildup bioinformatics computational pipelines allowed research explode. Several hundreds thousands conserved.9Salzman Gawad Wang Lacayo N. Brown P.O. predominant isoform genes diverse cell types.PLoS ONE. 2012; 7: e30733Crossref (1377) Scholar,10Hansen T.B. Jensen T.I. Clausen B.H. Bramsen J.B. Finsen Damgaard C.K. Kjems Natural circles function efficient microRNA sponges.Nature. 2013; 495: 384-388Crossref (3970) addition discovering new products, revised techniques specific detection without overlapping products. methods include RNase R treatment samples before sequencing, digests affecting resulting enrichment compared RNAs. Since 2017, databases annotation quantification established developed over time. On top powerful techniques, novel verification validation also developed.11Jeck W.R. Sharpless N.E. Detecting characterizing RNAs.Nat. Biotechnol. 2014; 32: 453-461Crossref (1368) adapted techniques. quantitative reverse transcriptase PCR, northern blot, and, later on, PCRs such digital PCR developed. made it possible wet laboratory scientists validate data dry laboratories. identification including vector expression plasmids siRNA silencing used overexpress knock down respectively, functions. situ hybridization pull-down assays underlying molecular circRNAs. With advent all able expand. More contributed conclusion simply actually hold critical physiological pathological during biological brief update We discuss localization translocation then bring insights into circRNA-based diagnostic strategies extensively conserved, stable, tissue-specific, subcellular location- stage-specific. direct where 3′ terminal directly joined 5′ precursor thereby proceed structure. This driven sequence (Figure 1A) RNA-binding (RBP) 1B). lariat-mediated model cut off forms lariat structure, further spliced 1C).12Kristensen L.S. Andersen M.S. Stagsted L.V.W. Ebbesen K.K. Hansen The biogenesis, biology characterization Rev. Genet. 2019; 20: 675-691Crossref (841) DDX39A DDX39B proteins export formed nucleus 1D). While usually transports short assists forming longer ones.13Huang Liang Tatomer D.C. Wilusz J.E. length-dependent pathway controls RNAs.Genes Dev. 2018; 639-644Crossref (116) Formed ordinarily stable owing exclusive defends cleavage exonuclease. undergo degradation. (A) (ICS)-driven model, intron regions both sides contain sequences, paired tightly connected promote (B) (RBP)-driven under bridging action RBP, sites at ends (C) lariat-driven back-splicing. (D) transport mature cytoplasm. (E–H) degradation (E) YTHDF2 recognizes m6A modification site circRNA. At same HRSP12 bridge P/MRP complex, initiating via P/MRP. (F) MicroRNA miR-671 mediates binding CDR1as AGO2 triggers regulated PKR activation. (G) Pathological exogenous double-stranded activate L cells degrade (H) complex UPF1 G3BP1 mediate (I) gene transcription, block genomic DNA, (J) serve miRNA decoy, inhibiting miRNAs. (K) inhibit activity functional domain. (L) combine complexes change activity. (M) translated polypeptides proteins. (N) Exosomes extracellular vesicles wrap secrete out cell. (O) Under certain conditions, take exosomes vesicles, intake recipient cells. Due cannot eliminated conventional pathways, half-life RNA. degraded, although fully understood. Theoretically, even though protects exonuclease cleavage, decay initiated endonucleases completed cascade exonucleases endonucleases. recent indicated N6-methylation adenosine (m6A) recognized HRSP12, reader protein, interact endonuclease trigger degradation14Park O.H. Ha Lee Boo S.H. Kwon D.H. Song H.K. Kim Y.K. Endoribonucleolytic m6A-containing complex.Mol. Cell. 74: 494-507.e8Abstract (143) 1E). mediated synthetic hairpin (shRNAs)/small interfering (siRNAs) conventionalmethod only example naturally occurring small RNA-mediated involves miR-671, has high complementarity induces AGO2-mediated degradation15Hansen Wiklund E.D. Villadsen S.B. Statham A.L. Clark S.J. miRNA-dependent involving Ago2-mediated antisense RNA.EMBO 30: 4414-4422Crossref (602) 1F). poly(I:C) stimulation encephalomyocarditis virus (EMCV) infection introduces (dsRNA) HeLa activates endoribonuclease L16Liu C.X. Li X. Nan F. Jiang S. Gao Guo S.K. Xue Cui Dong Ding al.Structure regulate activation innate immunity.Cell. 177: 865-880.e21Abstract (213) 1G). addition, there spontaneous peripheral blood mononuclear (PBMCs) derived patients systemic lupus erythematosus (SLE).16Liu Such L-mediated requires kinase (PKR) formation intra-dsRNA duplexes, activated cause global For secondary structures, structured ATP-dependent helicase upstream frameshift 1 (UPF1) G3BP1, subsequently induce degradation17Fischer J.W. Busa V.F. Shao Leung A.K.L. Structure-mediated G3BP1.Mol. 2020; 78: 70-84.e6Abstract (43) 1H). inside cells, exocytosis endocytosis occur discharge exosomes18Li Zheng Q. Bao Zhao Chen Gu He Huang enriched exosomes: promising biomarker diagnosis.Cell 2015; 25: 981-984Crossref (1107) Scholar,19Wang Ma Sun T. Zhou Wu al.Exosomal circRNAs: effect application diseases.Mol. Cancer. 18: 116Crossref (63) (Figures 1N 1O). shown present exosomes.19Wang Scholar,20Preußer Hung L.H. Schneider Schreiner Hardt Moebus A. Santoso Bindereif Selective release platelet-derived vesicles.J. Extracell. Vesicles. 1424473Crossref (98) cases, levels far those cells.18Li Scholar,21Dou Cha D.J. Franklin J.L. Higginbotham J.N. Jeppesen D.K. Weaver A.M. Prasad Levy Coffey Patton J.G. Zhang down-regulated KRAS mutant transferred exosomes.Sci. Rep. 2016; 6: 37982Crossref (198) Exosomal bind become cell-to-cell communication.22Bao Lyu expands its territory.Mol. Oncol. 3: e1084443Crossref (28) sum, lot remains unknown mediation signal communication, awaits addressed future investigations. mechanisms: regulating transcription 1I), acting (miRNA) sponges 1J), activities scaffolding 1K 1L), encoding 1M). Beyond fields, reviewed well.23Lim Lavenniah Foo R.S. Circles heart system.Cardiovasc. 116: 269-278PubMed Scholar, 24Aufiero Reckman Y.J. Pinto Y.M. Creemers E.E. open chapter biology.Nat. Cardiol. 16: 503-514Crossref (125) 25Lu Thum RNA-based disease.Nat. 661-674Crossref (86) 26Gomes C.P.C. Schroen Kuster G.M. Robinson E.L. Ford Squire I.B. Heymans Martelli Emanueli Devaux EU-CardioRNA COST Action (CA17129)Regulatory failure.Circulation. 141: 313-328Crossref (45) classify interesting developments 2). diagram shows relevant system. left column pink specifies dysfunction interest. middle orange indicates lead sponge mechanism. right green protein-binding most abundant cardiomyocytes circSLC8A1, plays myocardial hypertrophy caused pressure overload27Lim Aliwarga E. Luu T.D.A. Y.P. Ng S.L. Annadoray Sian Ackers-Johnson Targeting circSlc8a1 attenuates overload induced hypertrophy.Cardiovasc. 115: 1998-2007Crossref (47) Scholar,28Chen L.L. expanding Mol. Cell Biol. 475-490Crossref (157) damage ischemia-reperfusion29Li Tariq Chang Xu Hou ncx1 ischemic injury targeting miR-133a-3p.Theranostics. 8: 5855-5869Crossref (108) sponging miR-133a. angiotensin II-induced cardiac circRNA_000203 upregulated acts miR-26b-5p miR-140-3p, leading increased Gata4 aggravated hypertrophy.30Li Fang X.H. Zhu Yang Pan R. Yuan Zeng Z.Z. al.Circular aggravates suppressing miR-140-3p Gata4.Cardiovasc. 1323-1334Crossref (12) showed calcific aortic valve disease (CAVD), circRIC3 significantly upregulated, osteogenic trans-differentiation valvular interstitial circRIC3/miR-204-5p/DPP4 pathway, indicator accelerated calcification. It demonstrated melatonin inhibits expression, reducing calcification.31Wang Han Cao Melatonin ameliorates calcification regulation CircRIC3/miR-204-5p/DPP4 signaling cells.J. Pineal 69: e12666Crossref (3) Similarly, vascular smooth muscle overexpression circLRP6 promotes atherosclerosis development miR-145.32Hall I.F. Climent Quintavalle Farina F.M. Schorn Zani Carullo Kunderfranco Civilini Condorelli Elia circ_Lrp6, miRNA-145 function.Circ. 124: 498-510Crossref (72) Scholar,33Heumüller A.W. Dimmeler control functions.Circ. 456-458Crossref (7) muscle, circCHFR migration proliferation miR-370/FOXO1/cyclin D1 pathway;34Yang facilitates pathway.Mol. Ther. Nucleic Acids. 434-441Abstract (0) meanwhile, circNRG-1 apoptosis miR-193b-5p/NRG-1.35Sun Yue Bi Angiotensin II circNRG-1/miR-193b-5p/NRG-1 axis.Cell Death Dis. 10: 362Crossref (15) Not exert miRNA, activities. doxorubicin (Dox)-induced cardiotoxicity, miR-31-5p suppresses Quaking (QKI), RBP known influence production. As result, circPAN3 synthesis suppressed, leads cardiomyocyte apoptosis.36Ji MicroRNA-31-5p doxorubicin-induced cardiotoxicity quaking Pan3.J. 140: 56-67Abstract Besides classic mechanism, play roles modes action. cardiomyocytes, circFoxo3 higher older tissues younger tissues.37Du W.W. Z.K. Foster F.S. B.B. Foxo3 senescence modulating factors associated stress responses.Eur. Heart 2017; 38: 1402-1412Crossref interacts ID-1 E2F1, FAK, HIF-1α, anti-senescence anti-stress proteins, preventing transfer mitochondria, blocks downstream Dox-induced cardiomyopathy, cardiomyopathy.37Du super-enhancer-regulated circNfix adult hearts neonatal hearts. regulates Gsk3β miR-214, binds Y-box (Ybx1) E3 ubiquitin ligase (Nedd4l) interaction between Ybx1 result two action, suppressed. led promotion angiogenesis, reduced dysfunction, protected infarction (MI).38Huang Si Wei Liao al.Loss Nfix regeneration mice.Circulation. 139: 2857-2876Crossref (113) circFndc3b, whose decreased MI, similar function. Upregulation circFndc3b results enhancement reduction infarct size, improvement post-MI fused sarcoma (FUS) endothelial growth factor-A (VEGF-A).39Garikipati V.N.S. Verma Cheng Truongcao M.M. Cimini Benedict modulates repair FUS/VEGF-A axis.Nat. Commun. 4317Crossref (117) Lastly, autophagy-related (ACR) Dnmt3b, methylation Pink1 gene, promoting expression. phosphorylation FAM65B, death autophagy heart, ultimately protecting reperfusion injury.40Zhou L.Y. Zhai An Y.H. R.C. C.Y. al.The ACR ischemia/reperfusion modulation Pink1/FAM65B pathway.Cell Differ. 26: 1299-1315Crossref (89) van Heesch al.'s41van Witte Schneider-Lunitz V. Schulz J.F. Adami Faber A.B. Kirchner Maatz Blachut Sandmann C.L. translational landscape heart.Cell. 178: 242-260.e29Abstract (153) breakthrough discovery 80 translatomes least 39 ability encode newly detected ribosome-associated circCFLAR, circMYBPC3, circRYR2, CDR1as. authors identified bound ribosomes detect potential. Then, nucleic acid ribosome region junction confirm verified polypeptide (or microprotein) encoded six shotgun mass spectrometry. Translations 5 considered m6A-driven, while others likely IRES-driven.42Yang Fan Mao Jin al.Extensive translation N6-methyladenosine.Cell 27: 626-641Crossref (722) may organs besides liver kidney.41van peptides/microproteins uncovered, reveal diversity previously thought non-coding. Elucidating will increase understanding states heart. Even applied loads circRNA-mRNA started serving One consequence Cytoplasm facilitated circFoxo3, instance, aged mice patients, mentioned before, promoted vitro vivo. mainly localized cytoplasm, ID1 E2F1 (the proteins), FAK HIF1α retention affected act

Language: Английский

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Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 7

Published: Jan. 25, 2021

Unintended cardiac fibroblast proliferation in many pathophysiological heart conditions, known as fibrosis, results pooling of extracellular matrix (ECM) proteins the muscle. Transforming growth factor β (TGF-β) a pivotal cytokine/growth stimulates fibroblasts and hastens ECM production injured tissues. The TGF-β receptor is heterodimeric complex on plasma membrane, made up from type I, well II receptors, giving rise to Smad2 Smad3 transcription factors phosphorylation upon canonical signaling. Phosphorylated Smad2, Smad3, cytoplasmic Smad4 intercommunicate transfer signal nucleus, culminating provoked gene transcription. Additionally, activation starts non-canonical signaling that lead mitogen-stimulated protein kinase cascade activation, inducing p38, JNK1/2 (c-Jun NH2-terminal 1/2), ERK1/2 (extracellular signal–regulated 1/2) not only activates them differentiate into myofibroblasts, which produce proteins, but also promotes proliferation. Non-coding RNAs (ncRNAs) are important regulators numerous pathways along with cellular procedures. MicroRNAs circular long ncRNAs, combined capable affecting TGF-β/Smad signaling, leading fibrosis. More comprehensive knowledge based these processes may bring about new diagnostic therapeutic approaches for different disorders.

Language: Английский

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RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

Journal of Biomedical Science, Journal Year: 2020, Volume and Issue: 27(1)

Published: Jan. 3, 2020

Abstract Background Circular RNAs (circRNAs) represent a class of non-coding (ncRNAs) which are widely expressed in mammals and tissue-specific, some could act as critical regulators the atherogenesis cerebrovascular disease. However, underlying mechanisms by circRNA regulates ectopic phenotype endothelial cells (ECs) atherosclerosis remain largely elusive. Methods CCK-8, transwell, wound healing Matrigel assays were used to assess cell viability, migration tube formation. QRT-qPCR Immunoblotting examine targeted gene expression different groups. The binding sites miR-370-3p (miR-370) with TGFβR2 or hsa_circ_0003204 (circ_0003204) predicted using series bioinformatic tools, validated dual luciferase assay RNA immunoprecipitation (RIP) assay. localization circ_0003204 miR-370 ECs investigated fluorescence situ hybridization (FISH). Gene function pathways enriched through Metascape set enrichment analysis (GSEA). association extracellular vesicles (EVs) clinical characteristics patients multiple statistical analysis. Results Circ_0003204, mainly located cytoplasm human aorta (HAECs), was upregulated ox-LDL-induced HAECs. Functionally, inhibited proliferation, formation HAECs exposed ox-LDL. Mechanically, promote protein its downstream phosph-SMAD3 sponging miR-370, 3′ untranslated region (UTR) TGFβR2. Furthermore, plasma EVs cerebral atherosclerosis, represented potential biomarker for diangnosis prognosis atherogenesis. Conclusions Circ_0003204 novel stimulator inactivation atherosclerosis.

Language: Английский

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CircRNA‑0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting miR‑107

Molecular Medicine Reports, Journal Year: 2019, Volume and Issue: unknown

Published: March 6, 2019

Circular RNAs (circRNAs) are endogenous non‑coding implicated in atherosclerosis. The aim of the present study was to explore function circRNA‑0044073 Reverse transcription quantitative polymerase chain reaction assays were used measure expression levels circRNA‑0044073, microRNA (miRNA/miR)‑107, janus kinase 1 (JAK1), signal transducer and activator 3 (STAT3), B‑cell lymphoma 2 (Bcl‑2) v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) blood cells from patients with RNA pull‑down luciferase reporter then determine association between circRNA miR expression, gene respectively. Matrigel invasion assay flow cytometry analyze cell cycle. Western blot analysis ELISA evaluate proteins. It identified that upregulated miR‑107 downregulated atherosclerotic cells. Overexpression promoted proliferation human vascular smooth muscle (HUVSMCs) endothelial (HUVECs), while overexpression inhibited their proliferation. In addition, suppressed via a sponge mechanism. Lipopolysaccharide (LPS) affected HUVSMCs HUVECs, also resulted changes levels. CircRNA‑0044073 HUVECs spite opposite effect observed LPS treatment. JAK/STAT signaling pathway activated favored activation inflammation HUVECs. These data indicate is atherosclerosis promotes by targeting activating pathway, potentially offering target for novel treatment strategies against

Language: Английский

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Epigenetics in Cardiac Hypertrophy and Heart Failure

JACC Basic to Translational Science, Journal Year: 2019, Volume and Issue: 4(8), P. 976 - 993

Published: Dec. 1, 2019

Heart failure (HF) is a complex syndrome affecting millions of people around the world. Over past decade, therapeutic potential targeting epigenetic regulators in HF has been discussed extensively. Recent advances next-generation sequencing techniques have contributed substantial progress our understanding role DNA methylation, post-translational modifications histones, adenosine triphosphate (ATP)-dependent chromatin conformation and remodeling, non-coding RNAs pathophysiology. In this review, we summarize epigenomic studies on human animal models HF.

Language: Английский

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Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(13), P. 3140 - 3140

Published: June 27, 2019

Hyperhomocysteinemia (HHcy) exerts a wide range of biological effects and is associated with number diseases, including cardiovascular disease, dementia, neural tube defects, cancer. Although mechanisms HHcy toxicity are not fully uncovered, there has been significant progress in their understanding. The picture emerging from the studies homocysteine (Hcy) metabolism pathophysiology complex one, as Hcy its metabolites affect biomolecules processes tissue- sex-specific manner. Because connection to one carbon editing protein biosynthesis, impair epigenetic control gene expression mediated by DNA methylation, histone modifications, non-coding RNA, which underlies pathology human disease. In this review we summarize recent evidence showing that dysregulation expression, changes methylation N-homocysteinylation, pathogenic consequence many diseases. These findings provide new insights into disease induced metabolites, suggest therapeutic targets for prevention and/or treatment.

Language: Английский

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circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 8

Published: April 21, 2021

Circular RNA (circRNA) is a subclass of non-coding RNAs that enables the circular transcripts resistant to exonuclease digestion. Iron homeostasis essential for body maintain normal physiological functions. At present, relationship among circRNA, iron metabolism and heart failure remains largely unknown. This study aimed explore regulatory mechanism circRNA in failure. We obtained miRNA mRNA data from public databases built ceRNA network. The prediction results were verified myocardial tissues pressure overload-induced mice through use histopathological staining methods, malondialdehyde (MDA) measurement tests, quantitative real-time PCR (qRT-PCR), Western blot analysis luciferase reporter assay. A total 4 genes related oxidative stress identified, network involving 7 circRNAs, miRNAs, mRNAs was constructed using bioinformatics tools. qRT-PCR analyses indicated expression level FTH1 similar with predicted by analysis. Echocardiographic showed have lower fractional shortening ejection fraction. Moreover, myocardium displayed obvious fibrosis as well increased levels MDA compared control mice. Besides, circSnx12 could act an endogenous sponge bind miR-224-5p, 3'UTR region also had binding sites. circRNA-miRNA-mRNA successfully identifying differentially expressed metabolism. new approach reveals potential targets treatment

Language: Английский

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Circular RNAs in Cardiovascular Diseases: Regulation and Therapeutic Applications

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Cardiovascular disease is one of the leading causes mortality worldwide. Recent studies have shown that circular RNAs (circRNAs) emerged as important players in prevention and treatment cardiovascular diseases. circRNAs are a class endogenous noncoding generated by back-splicing involved many pathophysiological processes. In this review, we outline current research progress on regulatory roles Further, new technologies methods available for identifying, validating, synthesizing, analyzing circRNAs, well their applications therapeutics, highlighted here. Moreover, summarize increasing insights into potential use circulating diagnostic prognostic biomarkers. Finally, discuss prospects challenges circRNA therapeutic therapy, with particular focus developing synthesis engineering delivery systems.

Language: Английский

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