Oncogene, Journal Year: 2021, Volume and Issue: 40(15), P. 2756 - 2771
Published: March 13, 2021
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)
Published: Nov. 10, 2021
Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), are closely related variety biological functional aspects human health. When the exosomal ncRNAs undergo tissue-specific changes due diverse internal or external disorders, they can cause tissue dysfunction, aging, diseases. In this review, we comprehensively discuss underlying regulatory mechanisms exosomes in addition, explore current knowledge on roles miRNAs, lncRNAs, circRNAs health diseases, including cancers, metabolic neurodegenerative cardiovascular autoimmune infectious determine their potential implication biomarker identification therapeutic exploration.
Language: Английский
Citations
273
Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(10), P. 3133 - 3154
Published: April 9, 2022
Exosomes have a crucial role in intercellular communication and mediate interactions between tumor cells tumor-associated macrophages (TAMs). Exosome-encapsulated non-coding RNAs (ncRNAs) are involved various physiological processes. Tumor-derived exosomal ncRNAs induce M2 macrophage polarization through signaling pathway activation, signal transduction, transcriptional post-transcriptional regulation. Conversely, TAM-derived promote proliferation, metastasis, angiogenesis, chemoresistance, immunosuppression. MicroRNAs gene silencing by directly targeting mRNAs, whereas lncRNAs circRNAs act as miRNA sponges to indirectly regulate protein expressions. The of tumor-host is ubiquitous. Current research increasingly focused on the microenvironment. On basis "cancer-immunity cycle" hypothesis, we discuss effects immune T cell exhaustion, overexpression programmed death ligands, create immunosuppressive Furthermore, potential applications prospects clinical biomarkers drug delivery systems. 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Language: Английский
Citations
203
Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)
Published: April 9, 2021
Abstract Background A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development diseases through many mechanisms. The MAPK pathway is a common signal transduction involved cell proliferation, inflammation apoptosis plays particularly important role cancers. However, circRNAs related gastric cancer not explored. Methods bioinformatics analysis was performed profile identify cancer. tumor-suppressive circMAPK1 confirmed both vitro vivo. Mass spectrometry, Western blot immunofluorescence staining assays were used validate existence expression MAPK1–109aa. molecular mechanism investigated by mass spectrometry immunoprecipitation analyses. Results In this study, we identified that (hsa_circ_0004872) downregulated tissues compared with adjacent normal tissues. Importantly, lower predicted poor survival GC patients. CircMAPK1 inhibited proliferation invasion cells Next, found encoded protein 109 amino acids length. Through series functional experiments, exerted tumor-suppressing effect via Mechanistically, tumor suppressor MAPK1–109aa phosphorylation MAPK1 competitively binding MEK1, thereby suppressing activation its downstream factors pathway. Conclusions Our study revealed inhibits malignant biological behavior More importantly, favorable predictor for patients may provide new therapeutic target treatment
Language: Английский
Citations
176
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
Citations
143
Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(3), P. 1054 - 1070
Published: Jan. 14, 2022
Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported cancers, exosome-derived circRNAs rarely studied. In this work, we identified the differently expressed bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, immunoprecipitation, luciferase reporter assays were used to investigate interactions between specific circRNAs, microRNAs (miRNAs), mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), colony-formation study biological vitro. Metabolomics explore mechanism how influenced BCa cell behavior. Flow cytometry was affected function CD8+ T cells tumor microenvironments. We that hsa_circ_0085361 (circTRPS1) correlated with aggressive phenotypes via sponging miR-141-3p. sequencing (RNA-seq) GLS1-mediated glutamine metabolism involved circTRPS1-mediated alterations. derived from circTRPS1 knocked down cells, prevented exhaustion, repressed malignant phenotype cells. conclusion, can modulate intracellular reactive oxygen species (ROS) balance exhaustion circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker therapeutic target for BCa.
Language: Английский
Citations
121
Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)
Published: July 30, 2021
Exosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. derived from nearly all types cells and exist in body fluids. Noncoding RNAs (ncRNAs) among most abundant contents exosomes, some ncRNAs with functions specifically packaged into exosomes. Recent studies have revealed exosome-derived play crucial roles tumorigenesis, progression drug resistance gastric cancer (GC). In addition, regulating expression levels exosomal can or suppress GC progression. Moreover, membrane structures exosomes protect degradation by enzymes other chemical substances, significantly increasing stability ncRNAs. Specific hallmarks within be used for exosome identification, specific determine their origin. Therefore, suitable use as diagnostic prognostic biomarkers therapeutic targets. Regulating biogenesis may represent new way block eradicate GC. this review, we summarized origins characteristics analysed association between development.
Language: Английский
Citations
118
Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)
Published: Sept. 6, 2022
circRNA has been established to play a pivotal role in tumorigenesis development variety of cancers; nevertheless, the biological functions and molecular mechanisms hypoxia-induced exosomal circRNAs pancreatic cancer remain largely unknown.Differentially expressed exosomes between hypoxic normoxic PC cells were verified by RNA sequencing. The expression circPDK1 tumors patients was evaluated qRT-PCR ISH, through series vitro vivo experiments. Using Western blotting, Co-IP, pull-down, ChIP, RIP, dual-luciferase assays, rescue experiments, underlying mechanism verified.CircPDK1 highly abundant tumor tissues serum associated with poor survival. Exosomal significantly promoted cell proliferation, migration, glycolysis both vivo. Mechanistically, could be activated HIF1A at transcriptional level sponges miR-628-3p activate BPTF/c-myc axis. In addition, serves as scaffold that enhances interaction UBE2O BIN1, inducing UBE2O-mediated degradation BIN1.We found modulating miR-628-3p/BPTF axis degrading BIN1. is promising biomarker for diagnosis prognosis represents potential therapeutic target PC.
Language: Английский
Citations
101
Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)
Published: June 26, 2023
Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.
Language: Английский
Citations
99
Circulation Research, Journal Year: 2022, Volume and Issue: 130(6), P. 907 - 924
Published: Feb. 22, 2022
Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction penumbra existence after AIS crucial for making decision on reperfusion therapy. Yet fast, inexpensive, simple, noninvasive predictive biomarker the poststroke with clinical translational potential still lacking. We aim to investigate whether CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) in patients its role neuronal damage. Methods: was screened middle cerebral artery occlusion mice assessed plasma by quantitative polymerase chain reaction. Magnetic resonance imaging used examine volumes. interacted miR-5112 (microRNA-5112) primary cortical neurons detected fluorescence situ hybridization, immunoprecipitation, luciferase reporter assay. Adenovirus-mediated knockdown ameliorated apoptosis induced COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, Western blot were performed confirm exosomes. Results: expression dramatically selectively upregulated tissue 45 showing 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that positively correlated size AIS. Sequestering enhanced elevate neuron Additionally, significantly cell viability under conditions. Furthermore, brain closely related serum mice. Finally, we found highly expressed exosomes compared those individuals. Conclusions: These results demonstrate therapeutic target regulating viability, enriched neuron-derived peripheral blood, serving as
Language: Английский
Citations
91
The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(18)
Published: Sept. 2, 2022
Language: Английский
Citations
78