Biogenesis and Function of Circular RNAs in Health and in Disease

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: April 26, 2019

Circular RNAs (circRNAs) are a class of noncoding RNA that were previously thought to be insignificant byproducts splicing errors. However, recent advances in sequencing confirmed the presence circRNAs multiple cell lines and across different species suggesting functional role this species. CircRNAs arise from back-splicing events resulting circular is stable, specific conserved. They can generated exons, exon-introns, or introns. have multifaceted functions. likely part competing endogenous class. regulate gene expression by sponging microRNAs, binding proteins they translated into protein themselves. been associated with health disease, some disease protective effects, promoting The widespread regulatory mechanisms endow used as biomarkers therapeutic targets for variety disorders. In concise article we provide an overview association various diseases. addition their maintaining physiological cellular homeostasis discussed. We summary on fledgling body literature kidney-specific well cardiovascular circRNAs.

Language: Английский

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Circular RNA circ-PVT1 contributes to paclitaxel resistance of gastric cancer cells through the regulation of ZEB1 expression by sponging miR-124-3p

Bioscience Reports, Journal Year: 2019, Volume and Issue: 39(12)

Published: Dec. 1, 2019

Gastric cancer (GC) is the fifth most commonly diagnosed malignancy. Paclitaxel (PTX) an effective first-line chemotherapy drug in GC treatment, but resistance of PTX attenuates therapeutic effect. Circular RNA circ-PVT1 can exert oncogenic effect GC. But function involved still unknown. In present study, expression levels circ-PVT1, miR-124-3p and ZEB1 PTX-resistant tissues cells were detected by quantitative real-time polymerase chain reaction (RT-qPCR). was assessed 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The protein Zinc finger E-box binding homeobox 1 (ZEB1), P-glycoprotein (P-gp) glutathione S-transferase (GST-π) Western blot Cell apoptosis invasion measured flow cytometry transwell assays, severally. interaction between or predicted starBase software, then verified dual-luciferase reporter role vivo xenograft tumor model. Our results showed that up-regulated cells. Circ-PVT1 down-regulation enhanced sensitivity negatively regulating miR-124-3p. served as a direct target sponging knockdown increased vivo. Taken together, our studies disclosed facilitated up-regulating mediated via miR-124-3p, suggesting underlying strategy for

Language: Английский

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Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression

Journal of Experimental & Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 38(1)

Published: April 18, 2019

FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons FGFR3. However, potential functional hsa_circ_0068871 BCa remains largely unknown. Here we aim to evaluate BCa.We selected miR-181a-5p as target miRNA hsa_circ_0068871. The expression levels and were examined tissues paired adjacent normal by quantitative real-time PCR. To characterize function hsa_circ_0068871, cell lines stably infected with lentivirus targeting followed examinations proliferation, migration apoptosis. In addition, xenografts experiment nude mice performed effect BCa. Biotinylated RNA probe pull-down assay, fluorescence situ hybridization luciferase reporter assay conducted confirm relationship between FGFR3.Hsa_circ_0068871 over-expressed lines, whereas repressed. Depletion has_circ_0068871 or upregulation inhibited proliferation cells vitro vivo. Mechanistically, upregulated activated STAT3 promote progression.Hsa_circ_0068871 regulates miR-181a-5p/FGFR3 axis activates progression, it may serve biomarker.

Language: Английский

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A comprehensive review of circRNA: from purification and identification to disease marker potential

PeerJ, Journal Year: 2018, Volume and Issue: 6, P. e5503 - e5503

Published: Aug. 24, 2018

Circular RNA (circRNA) is an endogenous noncoding with a covalently closed cyclic structure. Based on their components, circRNAs are divided into exonic circRNAs, intronic and exon-intron circRNAs. CircRNAs have well-conserved sequences often high stability due to resistance exonucleases. Depending sequence, involved in different biological functions, including microRNA sponge activity, modulation of alternative splicing or transcription, interaction RNA-binding proteins, rolling translation, derivative pseudogenes. the development variety pathological conditions, such as cardiovascular diseases, diabetes, neurological cancer. Emerging evidence has shown that likely be new potential clinical diagnostic markers treatments for many diseases. Here we describe circRNA research methods discuss relationship between disease progression.

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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Molecular determinants of metazoan tricRNA biogenesis

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 47(12), P. 6452 - 6465

Published: April 18, 2019

Mature tRNAs are generated by multiple post-transcriptional processing steps, which can include intron removal. Recently, we discovered a new class of circular non-coding RNAs in metazoans, called tRNA intronic (tric)RNAs. To investigate the mechanism tricRNA biogenesis, constructs that replace native introns human and fruit fly genes with Broccoli fluorescent RNA aptamer. Using these reporters, identified cis-acting elements required for formation vivo. Disrupting conserved base pair anticodon-intron helix dramatically reduces levels. Although integrity this is necessary proper splicing, it not sufficient. In contrast, strengthening weak bases also interferes splicing production. Furthermore, trans-acting factors important including several known enzymes such as RtcB ligase components TSEN endonuclease complex. Depletion inhibits Drosophila circularization. Notably, missing from fungal genomes organisms normally produce linear introns. Here, show presence ectopic RtcB, yeast lacking Rlg1/Trl1 converted into producing tricRNAs. summary, our work characterizes major players eukaryotic biogenesis.

Language: Английский

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Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/β-catenin pathway

Neoplasma, Journal Year: 2018, Volume and Issue: 66(02), P. 232 - 239

Published: Dec. 4, 2018

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the of circ-ITCH TNBC and found was significantly down-regulated tissues cell lines closely associated with poor prognosis. We therefore constructed MDA-MB-231 BT-549 stably expressing by lentiviral vectors to determine underlying mechanisms progression. Most importantly, over-expression remarkably inhibited proliferation, invasion metastasis both vitro vivo. Mechanistically, acts as a sponge for miR-214 miR-17 increase expression ITCH linear isoform, thereby inactivating Wnt/β-catenin signaling. Our combined results show first time tumor suppressor, promising prognostic biomarker restoration could well be successful strategy TNBC.

Language: Английский

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CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis

Clinical Science, Journal Year: 2019, Volume and Issue: 133(9), P. 1053 - 1066

Published: April 16, 2019

Abstract Background: Circular RNAs (circRNAs) are a class of non-coding (ncRNAs) broadly expressed in cells various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) not well understood. In present study, we attempted to provide novel basis for targeted therapy LSCC from aspect circRNA–microRNA (miRNA)–mRNA interaction. Methods: We investigated expression three paired tissues and adjacent non-tumor by microarray analysis. Differentially were identified between non-cancerous matched tissues, including 527 up-regulated 414 down-regulated circRNAs. focused on hsa_circ_0059354, which is located chromosome 20 derived RASSF2, thus named it circRASSF2. Results: circRASSF2 was found be significantly lines compared non-tumorous normal cells. Moreover, knockdown inhibited proliferation migration vitro, blocked miR-302b-3p inhibitor. Bioinformatics analysis predicted there circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis progression. Dual-luciferase reporter system validated direct interaction circRASSF2, miR-302b-3p, IGF-1R. Western blot verified inhibition decreased IGF-1R expression. Furthermore, silencing suppressed vivo. Importantly, demonstrated serum exosomes patients. Altogether, suppresses progression interacting decreasing inhibiting Conclusion: conclusion, these data suggest central component linking via an miR-302b-3p/IGF-1R axis.

Language: Английский

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Long Noncoding RNA ANRIL: Lnc-ing Genetic Variation at the Chromosome 9p21 Locus to Molecular Mechanisms of Atherosclerosis

Frontiers in Cardiovascular Medicine, Journal Year: 2018, Volume and Issue: 5

Published: Nov. 6, 2018

Ever since the first genome-wide association studies (GWAS) on coronary artery disease (CAD), Chr9p21 risk locus has emerged as a top signal in GWAS of atherosclerotic cardiovascular disease, including stroke and peripheral disease. The CAD SNPs lie within stretch 58 kilobases non-protein-coding DNA, containing gene body long noncoding RNA (lncRNA) antisense non coding INK4 (ANRIL). How is affected by molecular detail matter ongoing research. Here we will review recent advances understanding that ANRIL serves key effector molecule atherogenesis at locus. One focus this shift genetic variation not only affects abundance ANRIL, some cases expression adjacent CDKN2A/B tumor suppressors, but also impacts splicing, such 3'-5'-linked circular species are produced. We describe how balance linear RNA, determined genotype, regulates pathways cellular functions involved atherogenesis. end with an outlook manipulating may be exploited for therapeutic purposes.

Language: Английский

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A novel circular RNA, hsa_circ_0046701, promotes carcinogenesis by increasing the expression of miR-142-3p target ITGB8 in glioma

Biochemical and Biophysical Research Communications, Journal Year: 2018, Volume and Issue: 498(1), P. 254 - 261

Published: Jan. 12, 2018

Language: Английский

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