CircRNA in cancer: Fundamental mechanism and clinical potential

Cancer Letters, Journal Year: 2021, Volume and Issue: 505, P. 49 - 57

Published: Feb. 18, 2021

Language: Английский

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Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Dec. 1, 2019

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for progression of non-small lung cancer (NSCLC) death NSCLC patients. Dysregulation circular RNAs plays a critical role in NSCLC; therefore, further understanding biological mechanisms abnormally expressed circRNAs is to discovering novel, promising therapeutic targets treatment. Methods The expression RNA fibroblast growth factor receptor 1 (circFGFR1) tissues, paired nontumor lines was detected by RT-qPCR. circFGFR1 assessed both vitro CCK-8, clonal formation, wound healing, Matrigel Transwell assays vivo subcutaneous mouse assay. In circRNA precipitation, immunoprecipitation, luciferase reporter were performed explore interaction between miR-381-3p. Results Here, we report that upregulated associated with deleterious clinicopathological characteristics poor prognoses Forced promoted migration, invasion, proliferation, immune evasion cells. Mechanistically, could directly interact miR-381-3p subsequently act as miRNA sponge upregulate target gene C-X-C motif chemokine 4 (CXCR4), which resistance anti-programmed (PD-1)- based therapy. Conclusion Taken together, our results suggest abilities cells provide new perspective on during progression.

Language: Английский

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Functions and clinical significance of circular RNAs in glioma

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Feb. 15, 2020

Abstract CircRNAs are a class of single-stranded RNA molecules with covalently closed loop structure and have been characterized by high stability, abundance, conservation, display tissue/developmental stage-specific expression, furthermore, based on the abundance in distinct body fluids or exosomes, circRNAs present novel biomarkers targets for diagnosis prognosis cancers. Recently, regulatory mechanisms biogenesis molecular functions, including miRNAs RBPs sponge, translation as well transcriptional splicing regulation, gradually uncovered, although various aspects remained to be elucidated combination deep-sequence bioinformatics. Accumulating studies indicated that more enriched neuronal tissues partly due specific genes promoting circularization, suggesting dysregulation is closely related diseases nervous system, glioma. In this review, we elaborate biogenesis, databases advances especially involved pathways, highlight its great value diagnostic therapeutic

Language: Английский

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The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(12), P. 911 - 946

Published: Nov. 1, 2020

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with closed loop structure. The majority circRNAs are formed by back-splicing process in pre-mRNA splicing. Their expression dynamically regulated and shows spatiotemporal patterns among cell types, tissues developmental stages. CircRNAs have important biological functions many physiological processes, their aberrant implicated human diseases. Due to high stability, becoming promising biomarkers diseases, such as cardiovascular autoimmune diseases cancers. In this review, we focus on the translational potential using blood liquid biopsy for We highlight abundant expression, essential significant correlations various components peripheral blood, including whole cells extracellular vesicles. addition, summarize current knowledge circRNA disease diagnosis or prognosis.

Language: Английский

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<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

OncoTargets and Therapy, Journal Year: 2020, Volume and Issue: Volume 13, P. 2067 - 2092

Published: March 1, 2020

Abstract: Circular RNA (circRNA) is an intriguing class of with covalently closed-loop structure and highly stable conservative. As new members the ncRNAs, function, mechanism, potential diagnostic biomarker, therapeutic target have raised increased attention. Most circRNAs are presented characteristics abundance, stability, conservatism, often exhibiting tissue/developmental-stage-specific manner. Over 30,000 been identified their unique structures to maintain stability more easily than linear RNAs. An numbers dysregulated involved in several biological processes malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, vascularization. Emerging evidence suggests that play important roles by acting miRNA sponge or protein scaffolding, autophagy regulators, interacting RNA-binding (RBP), which may potentially serve a novel promising biomarker for prevention, diagnosis treatment human cancer great significance either scientific research clinic arena. This review introduces concept, major features circRNAs, mainly describes functions clinical relevance well expressions regulatory mechanisms various types cancer, including pathogenesis, mode action, target, signaling pathways, drug resistance, biomarkers. All provide utilities cancer. Keywords: circRNA, sponge, gene splicing transcription,

Language: Английский

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Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 21, 2023

Despite advances in early detection and therapies, cancer is still one of the most common causes death worldwide. Since each tumor unique, there a need to implement personalized care develop robust tools for monitoring treatment response assess drug efficacy prevent disease relapse.

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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The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2021, Volume and Issue: 17(3), P. 291 - 306

Published: Feb. 7, 2021

Multi-drug resistance (MDR) is a hindrance toward the successful treatment of cancers. The primary mechanism that gives rise to acquired chemoresistance overexpression adenosine triphosphate-binding cassette (ABC) transporters. dysregulation non-coding RNAs (ncRNAs) widely concerned reason contributing this phenotype.In review, we describe role intracellular and exosomal ncRNAs including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs) in ABC transporters-induced tumor MDR. Meanwhile, will introduce potential therapeutic strategies which reverse MDR terms reducing expression transporters via targeting ncRNAs, like nucleic acid delivery with nanoparticles as well miRNAs-targeted small molecular compounds.The dysregulated ncRNAs-mediated chemo-resistant cancer not negligible. Finding out underlying may provide theoretical basis for clinical therapy MDR, emergence new approaches gene suppress makes reversing possible despite its application requires further investigations. Also, discovered regulating cancers are just tip iceberg genetic transcripts, especially circRNAs, justify more concern.Abbreviations: multi-drug resistance; ABC, cassette; NcRNAs, RNAs; MiRNAs, microRNAs; LncRNAs, CircRNAs, CeRNAs, competing endogenous 3'UTR, 3'-untranslated regions; SLC, solute carrier; ABCB1/MDR1, subfamily B member 1; ABCG2/BCRP, G 2; ABCCs/MRPs, C 1 12; DLL1: Delta-like protein DTX, docetaxel; DOX/ADM/ADR, doxorubicin/adriamycin; PTX, paclitaxel; VBL, vinblastine; VCR, vincristine; MTX, methotrexate; CDDP/DDP, cisplatin/cis-diaminedichloroplatinum; OXA/L-OHP, oxaliplatin; TMZ, temozolomide; 5-FU, 5-fluorouracil; MTA, pemetrexed; NSCLC, non-small cell lung carcinoma; HCC, hepatocellular CRC, colorectal RB, retinoblastoma; RCC, renal OS, osteosarcoma; PDAC, pancreatic ductal adenocarcinoma; TNBC, triple-negative breast cancer.

Language: Английский

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CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(3), P. e004029 - e004029

Published: March 1, 2022

Background Platinum resistance is a major challenge in the clinical treatment of advanced ovarian cancer (OC). Accumulating evidence shows that tumor-promotive M2 macrophage linked to limiting chemotherapy efficacy multiple malignancies including OC. Circular RNAs (circRNAs) are novel class non-coding which function as critical regulator biological process cancer. However, their impact on polarization and chemoresistance OC remain unclear. Methods Platinum-resistant circRNAs were screened using circRNA deep sequencing validated situ hybridization tissues with or without platinum resistance. The role circITGB6 inducing cisplatin (CDDP) was evaluated by clone formation, immunofluorescence annexin V assays vitro, intraperitoneal tumor model vivo. mechanism underlying circITGB6-mediated tumor-associated (TAM) into phenotype investigated RNA pull-down, luciferase reporter, electrophoretic mobility shift, binding protein immunoprecipitation (RIP), ELISA assays. Results We identified circRNA, circITGB6, robustly elevated serums from patients resistance, correlated poor prognosis. overexpression promoted an macrophage-dependent CDDP both vivo vitro. Mechanistic research determined directly interacted IGF2BP2 FGF9 mRNA form circITGB6/IGF2BP2/FGF9 RNA–protein ternary complex cytoplasm, thereby stabilizing TAMs toward phenotype. Importantly, blocking antisense oligonucleotide targeting markedly reversed circITGB6-induced Conclusions This study reveals for demonstrates may serve potential prognostic marker therapeutic target

Language: Английский

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CircGPR137B/miR-4739/FTO feedback loop suppresses tumorigenesis and metastasis of hepatocellular carcinoma

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: July 20, 2022

Abstract Background Emerging evidence indicates that circular RNAs (circRNAs) and m 6 A RNA methylation participate in the pathogenesis metastasis of multiple malignancies including hepatocellular carcinoma (HCC). However, it remains undocumented how circRNAs form a feedback loop with modification contributing to HCC. Methods novel hsa_circ_0017114 (circGPR137B) was identified from three pairs primary HCC adjacent normal tissues by circRNA expression profiling. The association circGPR137B miR-4739 clinicopathological parameters prognosis patients analyzed RT-qPCR, fluorescence situ hybridization TCGA cohorts. role estimated vitro vivo. western blot, dot RIP, MeRIP dual-luciferase reporter assays were used validate reciprocal regulation among circGPR137B, demethylase FTO. Meanwhile, expression, function FTO investigated rescue experiments. Results We new dramatically downregulated tissues, found downregulation or upregulation associated poor Ectopic strikingly repressed proliferation, colony formation invasion, whereas knockdown harbored opposite effects. Moreover, restored inhibited tumor growth lung Further investigations showed co-localized cytoplasm, acted as sponge for upregulate its target FTO, which mediated demethylation promoted expression. Thus, comprising circGPR137B/miR-4739/FTO axis formed. suppressed cell indicated favorable survival Conclusion Our results demonstrate inhibits tumorigenesis through loop. This positive mechanism executed functional coupling between an event suggests model epigenetics.

Language: Английский

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