Circular RNA and its mechanisms in disease: From the bench to the clinic

Pharmacology & Therapeutics, Год журнала: 2018, Номер 187, С. 31 - 44

Опубликована: Фев. 14, 2018

Язык: Английский

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Circular RNAs in Cancer

Molecular Therapy — Nucleic Acids, Год журнала: 2019, Номер 16, С. 118 - 129

Опубликована: Фев. 16, 2019

Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that formed by precursor mRNA back-splicing or skipping events thousands genes in eukaryotes as covalently continuous loops. High-throughput sequencing and bioinformatics approaches have uncovered the broad expression circRNAs across species. Their high stability, abundance, evolutionary conservation among species points to their distinct properties diverse cellular functions efficient microRNAs protein sponges; they also play important roles modulating transcription splicing. Additionally, most aberrantly expressed pathological conditions tissue-specific manner such development progression cancer. Herein, we highlight characteristics, functions, mechanisms action cancer; provide an overview recent progress circRNA field future application cancer biomarkers novel therapeutic targets. endogenous can form between downstream 3′ splice site upstream 5′ linear (pre-mRNA)1Chen L.L. The biogenesis emerging circular RNAs.Nat. Rev. Mol. Cell Biol. 2016; 17: 205-211Crossref PubMed Scopus (1005) Google Scholar transcribed polymerase II with same efficiency RNAs.2Chen Yang L. Regulation biogenesis.RNA 2015; 12: 381-388Crossref (1108) Advances (RNA-seq) tools resulted discovery identification various roles. First, reports indicated certain is highly specific cell type and/or developmental stage.3Panda A.C. Grammatikakis I. Kim K.M. De S. Martindale J.L. Munk R. X. Abdelmohsen K. Gorospe M. Identification senescence-associated (SAC-RNAs) reveals senescence suppressor CircPVT1.Nucleic Acids Res. 2017; 45: 4021-4035Crossref (153) Scholar, 4Chuang T.J. Wu C.S. Chen C.Y. Hung L.Y. Chiang T.W. M.Y. NCLscan: accurate non-co-linear transcripts (fusion, trans-splicing RNA) good balance sensitivity precision.Nucleic 44: e29Crossref (67) Second, lacking termini resistant degradation exonuclease RNase R more stable than associated mRNAs;1Chen therefore, higher concentration mRNAs present quiescent post-mitotic cells.5Han B. Chao J. Yao H. its disease: from bench clinic.Pharmacol. Ther. 2018; 187: 31-44Crossref (419) because level stability blood other body fluids, considered potential for risk prediction. Third, genome-wide analyses levels abundance species.6Jeck W.R. Sorrentino J.A. Wang Slevin M.K. Burd C.E. Liu Marzluff W.F. Sharpless N.E. abundant, conserved, ALU repeats.RNA. 2013; 19: 141-157Crossref (2610) 7Du W.W. Fang W. N. Awan F.M. Z. B.B. Induction tumor apoptosis through enhancing Foxo3 activity.Cell Death Differ. 24: 357-370Crossref (378) might act miRNA sponges competing RNA, bind sequester proteins, modulate splicing.1Chen 8Qu Zhou Yu Zhang Li cancer.Cancer Lett. 414: 301-309Crossref (181) Thus, significant pathogenesis great cancer, likely involved many hallmarks cancer.9Bach D.-H. Lee S.K. Long noncoding cells.Cancer 419: 152-166Crossref (117) will critical perspective, including possible role targets derived pre-mRNAs, thus modulation may require canonical spliceosomal machinery.10Huang G. Zou Y. Zheng D. Xiao T. Recent human cancers.Cancer 404: 8-18Crossref (82) However, not fully understood. originate exons coding regions UTR, antisense RNAs, intergenic regions, introns.11Dong He Peng Shi C. Duan cancer: key player.J. Hematol. Oncol. 10: 2Crossref (189) 12Li Q. Bao Guo Zhao Gu Huang enriched exosomes: promising biomarker diagnosis.Cell 25: 981-984Crossref (1340) Among them, cells mainly single several exons, so-called exonic (ecircRNAs)10Huang account over 80% identified circRNAs.11Dong Although alternative splicing, particular exon skipping, major modulator production, main mechanism which remains elusive. be different splicing RNAs; gene locus produce variety back-splice selection.11Dong 13Zhang X.O. Dong Luo Diverse landscape RNAs.Genome 26: 1277-1287Crossref (472) Up now, three types been high-throughput sequencing: intronic (ciRNAs), contain introns only; exon-intron cirRNAs (EIciRNAs), both exons; tRNA (tricRNAs), via pre-tRNA splicing.10Huang RNA-seq helped identify numerous model organisms types,14Szabo Salzman Detecting RNAs: bioinformatic experimental challenges.Nat. Genet. 679-692Crossref (392) some internal ribosome entry elements AUG sites.15Pamudurti N.R. Bartok O. Jens Ashwal-Fluss Stottmeister Ruhe Hanan Wyler E. Perez-Hernandez Ramberger et al.Translation CircRNAs.Mol. Cell. 66: 9-21.e7Abstract Full Text PDF (987) there currently limited evidence translation vivo,6Jeck biological remain unknown.10Huang 16Kristensen L.S. Hansen T.B. Venø M.T. Kjems opportunities challenges field.Oncogene. 37: 555-565Crossref (827) studies shown function modulators transcription; few translated into peptides implying at multiple levels. miRNAs direct base pairing target sites within known processes, 17Bach Hong J.-Y. Park H.J. exosomes drug-resistance cells.Int. Cancer. 141: 220-230Crossref (163) 18Bach dual bone morphogenetic proteins cancer.Mol. Oncolytics. 8: 1-13Abstract (89) 19Bach D.H. N.P. Luu T.T. Anh N.H. Kwon S.W. dominant forkhead box cancer.Int. Sci. E3279Crossref (1) 20Bach Bae S.Y. W.K. J.Y. Rajasekaran Fan al.Targeting Nicotinamide N-Methyltransferase miR-449a EGFR-TKI-resistant non-small-cell lung cells.Mol. Nucleic Acids. 11: 455-467Abstract (45) Most predominantly located cytoplasm,1Chen suggesting competitive activity miRNA-binding sites.16Kristensen 21Hansen Jensen T.I. Clausen B.H. Bramsen J.B. Finsen Damgaard C.K. Natural circles microRNA sponges.Nature. 495: 384-388Crossref (4720) al.22Li F. Deng An Lu ITCH has inhibitory effect on ESCC suppressing Wnt/β-catenin pathway.Oncotarget. 6: 6001-6013Crossref (561) itchy E3 ubiquitin ligase (cir-ITCH) suppressed growth acting sponge increased ITCH. al.23Chen Lyu Xu al.Circular profile identifies circPVT1 proliferative factor prognostic marker gastric 388: 208-219Crossref reported stimulate playing members miR-125 family.16Kristensen Importantly, ciRS-7, designated miR-7 inhibitor reducing increasing miR-7-targeted transcripts, conceptually changed mechanistic understanding networks.24Hansen 73: 5609-5612Crossref (725) In situ profiling was remarkable overlap ciRS-7 mouse brain, majority brain-expressed tethered ciRS-7.24Hansen Hence, abundant ciRS-7/miR-7 correlation contribute pool available RNA-induced silencing complex components.24Hansen Consequently, generally less pronounced ciRS-7/miR-7-expressing tissues.24Hansen could miRNAs.16Kristensen 25Guo J.U. Agarwal V. Bartel D.P. Expanded characterization mammalian 2014; 15: 409Crossref (1057) suggested restricted nucleus,1Chen similar observation nuclear restriction containing retained introns, large number post-transcriptional modulators.26Braunschweig U. Barbosa-Morais N.L. Pan Nachman E.N. Alipanahi Gonatopoulos-Pournatzis Frey Irimia Blencowe B.J. Widespread intron retention mammals functionally tunes transcriptomes.Genome 1774-1786Crossref 27Memczak Elefsinioti A. Torti Krueger Rybak Maier Mackowiak S.D. Gregersen L.H. Munschauer animal regulatory potency.Nature. 333-338Crossref (4733) contrast back-spliced ciRNAs associate insoluble fraction little enrichment miRNAs.28Zhang Xiang J.F. Yin Q.F. Xing Y.H. Zhu long RNAs.Mol. 51: 792-806Abstract (1422) Significantly, knockdown lead reduced parent genes, eliciting one positive (Pol II) transcription.28Zhang found ci-Ankyrin Repeat Domain 52 (ci-ANKRD52), interact elongation Pol largely accumulates sites, stimulates parental ANKRD52.28Zhang al.29Li Lin Zhong Hu Dai al.Exon-intron regulate nucleus.Nat. Struct. 22: 256-264Crossref (1686) EIciRNA-U1 small ribonucleoprotein (snRNP) complexes U1 snRNP EIciRNAs, special circRNAs, hold factors RNA-RNA interaction, further promoters expression. physiological processes binding decoys sponges. best experimentally supported example mannose-binding lectin (MBL) locus.16Kristensen MBL significantly contributes circMBL, this dependent sites.30Ashwal-Fluss Meyer Pamudurti Ivanov Evantal Memczak Rajewsky Kadener competes pre-mRNA splicing.Mol. 56: 55-66Abstract (1796) circFOXO3 regulation protein-protein interactions.7Du 31Du Yong Identifying characterizing circRNA-protein interaction.Theranostics. 7: 4183-4191Crossref (339) circ-FOXO3 p53 MDM2, enhance breast cisplatin doxorubicin.31Du Schneider al.32Schneider Schreiner Starke Eckhof Rossbach Reich Medenbach Bindereif CircRNA-protein complexes: IMP3 component defines subfamily circRNPs.Sci. Rep. 31313Crossref (98) focused (IGF2BP3 [Insulin-Like Growth Factor 2 Binding Protein 3]), RNA-binding marker, investigate circRNPs component. They circRNP families exist defined common Both these demonstrated dynamics interaction tissues frequently applied transcriptome studies, especially deep samples investigating cataloguing alterations structure transcriptomes.33Salzman Gawad P.L. Lacayo Brown P.O. predominant transcript isoform hundreds types.PLoS ONE. 2012; e30733Crossref (1598) tissue- stage-specific expression, abundantly hematopoietic compartment.34Bonizzato Gaffo Te Kronnie Bortoluzzi CircRNAs hematopoiesis hematological malignancies.Blood Cancer e483Crossref (109) Platelets small, translationally competent, circulating megakaryocytes35Haemmerle Stone R.L. Menter D.G. Afshar-Kharghan Sood A.K. platelet lifeline opportunities.Cancer 33: 965-983Abstract (217) hemostasis, angiogenesis, wound healing.36Garraud Cognasse Are platelets cells? And if yes, immune cells?.Front. Immunol. 70Crossref capable mature mRNAs.35Haemmerle Alhasan al.37Alhasan A.A. Izuogu O.G. Al-Balool H.H. Steyn J.S. Evans Colzani Ghevaert Mountford J.C. Marenah Elliott D.J. signature degradation.Blood. 127: e1-e11Crossref (139) platelets, where generated compared nucleated types. Several were using selectively remove relative proportion cultured megakaryocytes lower platelets.38Sunderland Skroblin P. Barwari Huntley R.P. Joshi Lovering R.C. Mayr MicroRNA reactivity: clot thickens.Circ. 120: 418-435Crossref (125) primary patient malignancies, gaining insight biology knowledge how mRNAs.38Sunderland packaged released vesicles (exosomes microvesicles) (Figure 1).17Bach 39Preußer L.-H. Hardt Moebus Santoso Selective release platelet-derived extracellular vesicles.J. Extracell. Vesicles. 1424473Crossref (119) 40Yang Fu Exosomal non-coding biomarker.Clin. Chem. Lab. Med. 54: 1871-1879Crossref (12) 41Bach T.-T.-T. Y.J. BMP4 upregulation acquired drug resistance fatty acid metabolism EGFR-mutant 817-828Abstract (0) widely cells.42Dou Cha Franklin Higginbotham J.N. Jeppesen D.K. Weaver A.M. Prasad Levy Coffey R.J. Patton J.G. down-regulated KRAS mutant colon transferred exosomes.Sci. 37982Crossref (231) Sorting modulated changes producer cells, recipient 1).12Li observed secreted colorectal provided peripheral whole blood,43Memczak Papavasileiou Peters new putative blood.PLoS e0141214Crossref (447) components useful biomarker.44Qian Lv Xie Bai al.Potential diagnostic power active pulmonary tuberculosis.EBioMedicine. 27: 18-26Abstract (47) Qian al.44Qian wide mononuclear (PBMCs), comparable landscapes blood. difference PBMCs patients tuberculosis healthy controls.44Qian al.45Zhao Gao Jian Hao Rao Peripheral hsa_circ_0124644 used coronary artery disease.Sci. 39918Crossref (168) analyzed disease (CAD) control individuals microarray. five all CAD group, hsa-circ-0124644 had largest area under curve.45Zhao Guarnerio al.46Guarnerio Bezzi Jeong Paffenholz S.V. Berry Naldini M.M. Lo-Coco Tay Beck A.H. Pandolfi P.P. Oncogenic fusion-circRNAs cancer-associated chromosomal translocations.Cell. 165: 289-302Abstract fusion translocations.16Kristensen tumor-associated translocations, mixed lineage leukemia (MLL)-AF9 acute myeloid (AML) promyelocytic leukemia-retinoic receptor-alpha (PML-RARA) leukemia, named (f-circRNAs). f-circRNAs (f-circPR f-circM9) promote viability, transformation upon therapy, biologically exert pro-proliferative pro-oncogenic activities.46Guarnerio MLL-AF9-derived stimulated p27 p21 THP1 viability.47Alderton G.K. Translocations: translocations.Nat. 16: 273Google To consider aspects biology, existing context 48Hanahan Weinberg R.A. Hallmarks next generation.Cell. 2011; 144: 646-674Abstract (40224) serve regulators sustained signaling. One examples circ-FOXO3, decreased tumors affect FOXO3, p53, PUMA expression.7Du Sco

Язык: Английский

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Circular RNAs open a new chapter in cardiovascular biology

Nature Reviews Cardiology, Год журнала: 2019, Номер 16(8), С. 503 - 514

Опубликована: Апрель 5, 2019

Язык: Английский

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Roles of circRNAs in the tumour microenvironment

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Янв. 23, 2020

Abstract The tumour microenvironment (TME) constitutes the area surrounding during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with cells. Circular RNAs (circRNAs) are a subpopulation of endogenous noncoding (ncRNAs) that ubiquitously expressed eukaryotes have multiple biological functions regulation cancer onset progression. An increasing number studies shown circRNAs participate multifaceted TME. However, details on mechanisms involved remained elusive until now. In this review, we analyse effects TME from various perspectives, including immune surveillance, angiogenesis, hypoxia, matrix remodelling, exo-circRNAs chemoradiation resistance. Currently, enormous potential for circRNA use targeted therapy as noninvasive biomarkers drawn our attention. We emphasize prospect targeting an essential strategy regulate TME, overcome resistance improve therapeutic outcomes.

Язык: Английский

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Non-coding RNAs in cardiovascular cell biology and atherosclerosis

Cardiovascular Research, Год журнала: 2019, Номер 115(12), С. 1732 - 1756

Опубликована: Авг. 5, 2019

Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause morbidity mortality worldwide. The development, progression formation clinically relevant atherosclerotic plaques involves interaction distinct over-lapping mechanisms which dictate roles actions multiple resident recruited cell types including endothelial cells, vascular smooth muscle monocyte/macrophages. discovery non-coding RNAs (ncRNAs) microRNAs, long RNAs, circular their identification as key mechanistic regulators mRNA protein expression has piqued interest in potential contribution to atherosclerosis. Accruing evidence revealed ncRNAs regulate pivotal cellular molecular processes during all stages atherosclerosis invasion, growth, survival; uptake efflux lipids, release pro- anti-inflammatory intermediaries, proteolytic balance. profile within lesions circulation have been determined with aim identifying individual or clusters may be viable therapeutic targets alongside deployment biomarkers plaque progression. Consequently, numerous vivo studies convened determine effects moderating function select well-characterized animal models Together, clinicopathological findings elucidated multifaceted frequently divergent impose both directly indirectly on From these findings' novel strategies discovered pave way for further translational possibly taken forward clinical application.

Язык: Английский

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FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma

Journal of Experimental & Clinical Cancer Research, Год журнала: 2019, Номер 38(1)

Опубликована: Фев. 8, 2019

Angiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate regulation malignant behaviors tumors. As type endogenous non-coding RNAs, circular (circRNAs) are abnormally expressed various cancers involved diverse tumorigeneses including angiogenesis.The expression levels FUS, circ_002136, miR-138-5p, SOX13, SPON2 were determined using quantitative real-time PCR (qRT-PCR) western blot. Transient cell transfection was performed Lipofectamine 3000 reagent. The protein immunoprecipitation (RNA-IP) RNA pull-down assays used to detect interaction between FUS circ_002136. dual-luciferase reporter assay system binding sites circ_002136 miR-138-5p SOX13. chromatin (ChIP) examine interactions transcription factor SOX13 its target .We demonstrated down-regulation or dramatically inhibited viability, migration tube formation U87 glioma-exposed endothelial cells (GECs). MiR-138-5p down-regulated GECs functionally targeted an RNA-induced silencing complex (RISC). Inhibition combined restoration robustly reduced angiogenesis GECs. gene overexpressed proved be miR-138-5p-mediated gliomas. In addition, we found directly associated activated promoter, thereby up-regulating at transcriptional level. Knockdown suppressed More important, promoter increased expression, forming feedback loop.Our data suggests loop FUS/circ_002136/miR-138-5p/SOX13 played crucial This also provides potential alternative strategy for glioma therapy.

Язык: Английский

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Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

Theranostics, Год журнала: 2021, Номер 11(8), С. 3996 - 4010

Опубликована: Янв. 1, 2021

Exosomes are nanosized lipid vesicles originating from the endosomal system that carry many macromolecules their parental cells and play important roles in intercellular communication. The functions underlying mechanisms of exosomes atherosclerosis have recently been intensively studied. In this review, we briefly introduce exosome biology then focus on advances atherosclerosis, specifically exosomal changes associated with cellular origins potential functional cargos, detailed impacts recipient cells. We also discuss as biomarkers drug carriers for managing atherosclerosis.

Язык: Английский

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Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits

Aging, Год журнала: 2018, Номер 10(9), С. 2266 - 2283

Опубликована: Сен. 6, 2018

Atherosclerosis is a chronic and multifactorial inflammatory disease closely associated with cardiovascular cerebrovascular diseases. circRNAs can act as competing endogenous RNAs to mRNAs function in various However, there little known about the of atherosclerosis. In this study, three rabbits case group were fed high-fat diet induce atherosclerosis another normal diet. To explore biological functions atherosclerosis, we analyzed circRNA, miRNA mRNA expression profiles using RNA-seq. Many miRNAs, identified significantly changed We next predicted miRNA-target interactions miRanda tool constructed differentially expressed circRNA-miRNA-mRNA triple network. A gene ontology enrichment analysis showed that genes network involved cell adhesion, activation immune response. Furthermore, generated dysregulated circRNA-related ceRNAs found seven (ocu-cirR-novel-18038, -18298, -15993, -17934, -17879, -18036 -14389) related these also functioned These results show crosstalk between their might play crucial roles development

Язык: Английский

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Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Pharmacology & Therapeutics, Год журнала: 2018, Номер 196, С. 15 - 43

Опубликована: Ноя. 13, 2018

Язык: Английский

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Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway

Molecular Therapy — Nucleic Acids, Год журнала: 2019, Номер 16, С. 434 - 441

Опубликована: Апрель 6, 2019

Язык: Английский

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