Roles of circRNAs in the tumour microenvironment

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

Published: Jan. 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.

Language: Английский

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Identification of Serum Exosomal hsa-circ-0004771 as a Novel Diagnostic Biomarker of Colorectal Cancer

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

Published: Nov. 1, 2019

Background: Exosomal circular RNAs (circRNAs) in peripheral blood are considered as emerging diagnostic biomarkers of cancers. Owing to the lack sensitive and specific biomarkers, a large number colorectal cancer (CRC) patients were diagnosed advanced stages leading high mortality. This study aimed identify circulating exosomal circRNAs novel CRC. Materials Methods: Candidate circRNA was selected by integrating analysis Gene Expression Omnibus (GEO) database with online program GEO2R. A total 170 45 healthy controls enrolled assess value for Exosomes isolated from serum participants cell cultured media confirmed transmission electron microscope (TEM), Nanoparticle Tracking Analysis western blot. The expression utility tested qRT-PCR receiver operating characteristic (ROC) analysis, respectively. Results: hsa-circ-0004771 most abundant among top ten differentially expressed (fold change ≥1.5) further based on results GEO dataset analysis. up-regulated verified CRC compared (HCs) benign intestinal diseases (BIDs) qRT-PCR. area under ROC curves (AUCs) 0.59 (95%CI, 0.457-0.725), 0.86 0.785-0.933) 0.88 0.815-0.940) differentiate BIDs, stage I/II HCs, AUC 0.816 0.728-0.9) BIDs. In addition, elevated tumor-derived. It found that down-regulated postoperative well cells treated GW4869. Conclusions: Circulating significantly served potential biomarker

Language: Английский

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CircSMARCA5 Regulates VEGFA mRNA Splicing and Angiogenesis in Glioblastoma Multiforme Through the Binding of SRSF1

Cancers, Journal Year: 2019, Volume and Issue: 11(2), P. 194 - 194

Published: Feb. 7, 2019

Circular RNAs are a large group of whose cellular functions still being investigated. We recently proposed that circSMARCA5 acts as sponge for the splicing factor Serine and Arginine Rich Splicing Factor 1 (SRSF1) in glioblastoma multiforme (GBM). After demonstrating by RNA immunoprecipitation physical interaction between SRFS1 circSMARCA5, we assayed real-time PCR cohort 31 GBM biopsies 20 unaffected brain parenchyma controls (UC) expression total, pro-angiogenic (Iso8a) anti-angiogenic (Iso8b) mRNA isoforms Vascular Endothelial Growth A (VEGFA), known target SRSF1. The Iso8a to Iso8b ratio: (i) increased with respect UC (p-value < 0.00001); (ii) negatively correlated (r-value = −0.46, p-value 0.006); (iii) decreased U87-MG overexpressing negative control 0.0055). Blood vascular microvessel density, estimated within same biopsies, −0.59, 0.00001), while positively SRSF1 0.38, 0.00663) ratio 0.41, 0.0259). Kaplan-Meier survival analysis showed patients low had lower overall progression free rates than those higher (p-values 0.033, 0.012, respectively). Our data convincingly suggest is an upstream regulator pro- VEGFA cells highly promising prognostic prospective molecule.

Language: Английский

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Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role

Critical Reviews in Oncology/Hematology, Journal Year: 2019, Volume and Issue: 145, P. 102854 - 102854

Published: Dec. 20, 2019

Language: Английский

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Transcriptome-wide profiles of circular RNA and RNA-binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: Dec. 1, 2020

Circular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown bind RNA-binding proteins (RBPs); however, little is known about the prevalence and distribution of these interactions in different biological contexts.We conduct an extensive screen circRNA-RBP ENCODE cell lines HepG2 K562. We profile deep-sequenced total samples analyze using a large set eCLIP data binding sites 150 RBPs. validate for select RBPs by performing immunoprecipitation functionally characterize our most interesting candidates conducting knockdown studies followed RNA-Seq.We generate comprehensive catalog K562 cells. show that KHSRP enriched flanking introns depletion affects circRNA biogenesis. identify covered RBP experimentally individual interactions. circCDYL, clinical functional implications bladder cancer, almost completely GRWD1 cells, circCDYL counteracts effect depletion. Furthermore, we confirm between cancer cells demonstrate hallmarks perturbs expression key genes, e.g., TP53. Finally, elevated levels associated overall survival patients.Our study demonstrates transcriptome-wide cell-type-specific could play important roles tumorigenesis.

Language: Английский

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Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 24, 2021

Circular RNAs (circRNAs), covalently closed noncoding RNAs, are widely expressed in eukaryotes and viruses. They can function by regulating target gene expression, linear RNA transcription protein generation. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays key roles many biological cellular processes, such as cell proliferation, growth, invasion, migration, angiogenesis. It also a pivotal role cancer progression. Emerging data suggest that the circRNA/PI3K/AKT axis modulates expression of cancer-associated genes thus regulates tumor Aberrant regulation circRNAs is significantly associated with clinicopathological characteristics an important functions. In this review, we summarized functions PI3K-AKT-related vitro vivo assessed their associations characteristics. We further discussed diagnosis, prognostication, treatment cancers.

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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Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p

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

Published: Jan. 5, 2022

Abstract Background More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs prostate cancer (PCa) remains largely unknown. Methods Differentially expressed were identified by RNA sequencing. The expression hsa_circ_0003258 was evaluated using quantitative real-time PCR situ hybridization. impacts on metastasis PCa cells investigated series vitro vivo assays. Lastly, underlying revealed Western blot, biotin-labeled pulldown, immunoprecipitation, luciferase assays rescue experiments. Results Increased found tissues associated with advanced TNM stage ISUP grade. Overexpression promoted cell migration inducing epithelial mesenchymal transformation (EMT) as well tumor , while knockdown exerts opposite effect. Mechanistically, could elevate Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, physically binds to insulin like growth factor 2 mRNA binding 3 (IGF2BP3) cytoplasm enhanced HDAC4 stability, which it activates ERK signalling pathway, then triggers EMT programming finally accelerates PCa. Conclusions Upregulation drives progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act promising biomarker for an attractive target intervention.

Language: Английский

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Arabidopsis apoplastic fluid contains sRNA- and circular RNA–protein complexes that are located outside extracellular vesicles

The Plant Cell, Journal Year: 2022, Volume and Issue: 34(5), P. 1863 - 1881

Published: Feb. 3, 2022

Previously, we have shown that apoplastic wash fluid (AWF) purified from Arabidopsis leaves contains small RNAs (sRNAs). To investigate whether these sRNAs are encapsulated inside extracellular vesicles (EVs), treated EVs isolated with the protease trypsin and RNase A, which should degrade located outside but not those inside. These analyses revealed mostly associated proteins. Further of (exRNAs) they include both long noncoding (lncRNAs), including circular (circRNAs). We also found exRNAs highly enriched in posttranscriptional modification N6-methyladenine (m6A). Consistent this, identified a putative m6A-binding protein AWF, GLYCINE-RICH RNA-BINDING PROTEIN 7 (GRP7), as well sRNA-binding ARGONAUTE2 (AGO2). two proteins coimmunoprecipitated lncRNAs, circRNAs. Mutation GRP7 or AGO2 caused changes sRNA lncRNA content suggesting contribute to secretion and/or stabilization exRNAs. propose mediate host-induced gene silencing, rather than RNA EVs.

Language: Английский

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POSTAR3: an updated platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D287 - D294

Published: Aug. 14, 2021

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation. Accurate identification of RBP binding sites multiple cell lines and tissue types from diverse species is a fundamental endeavor towards understanding the regulatory mechanisms RBPs under both physiological pathological conditions. Our POSTAR annotation processes make use publicly available large-scale CLIP-seq datasets external functional genomic annotations to generate comprehensive map their association with other events as well variants. Here, we present POSTAR3, an updated database improvements data collection, infrastructure, analysis that support regulation including: made update on Ribo-seq which cover more biological conditions, technologies, species; added RNA secondary structure profiling for sites; provided miRNA-mediated degradation validated by degradome-seq; included at circRNA junction regions; expanded sites, particularly using variants mutations associated diseases. POSTAR3 freely http://postar.ncrnalab.org.

Language: Английский

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