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Extracellular vesicles (EVs) are a kind of exsomes secreted by cells, which all cells release them as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories by their sizes, small EVs (sEVs) and medium/large EVs (m/l EVs). As a kind of extracellular vesicle, sEVs are mostly discoid vesicles with diameters ranging from 40 nm to 200 nm. The medium/large EVs are elliptical with a diameter more than 200 nm. sEVs play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of liver diseases. In this review, we discussed the current understanding of the role of sEVs, particularly sEV derived non-coding RNA in non-alcoholic fatty liver disease (NAFLD) and their potential as diagnostic and therapeutic targets. sEVs are small membrane-bound particles secreted by cells, which fuse with plasma membrane and release to extracellular matrix. Depending on the cell of origin, sEVs could contain many cell constituents, including various DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins, biomolecules. In addition, many RNA and DNA molecules contained by sEVs, such as mRNA, microRNA (miRNA), long noncoding RNA (lncRNA) and mitochondrial DNA (mtDNA), can be transferred to recipient cells to effectively promote their biological response, physiological and pathological functions. Such sEVs-mediated responses can be disease promoting or restraining. The intrinsic properties of sEVs in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in sEVs, suggesting that they have a role in regulating intercellular communication. Many studies have also shown the involvement of sEVs’ noncoding RNAs (ncRNAs) in controlling cell activities and their crucial functions in regulating lipid metabolism. sEVs ncRNAs, including miRNAs, lncRNAs, and circular RNAs (circRNAs) regulate physiological functions and maintain lipid metabolism homeostasis. miRNA are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messenger RNA-targets. These circulating miRNAs are easily accessible, disease-specific and sensitive to small changes, which makes them ideal biomarkers for diagnostic, prognostic, predictive or monitoring purposes. Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response in liver diseases. And lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. Then circRNAs contributed to NAFLD progression by acting as miRNA sponges, functional protein sponges, or novel templates for protein translation. Finally, sEVs could be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides and so on, with an ability to direct their delivery to a desired target. The potential of targeting sEVs with lncRNAs and miRNAs not only could be potential diagnostic biomarkers for NAFLD, but also have potential therapeutic effects on NAFLD, which might provide new ideas for the NAFLD treatment. In conclusion, this review provides an overview of the current understanding of the roles of sEVs ncRNAs in NAFLD, so we suggest that further research into sEVs could lead to new diagnostic tools and therapeutic strategies for NAFLD.
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Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.
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BACKGROUND:The pathogenesis of autoimmune hepatitis has not been clearly elucidated.Circular RNA(CircRNA)is a research hotspot in the field of RNA and is involved in the pathogenesis of many autoimmune diseases.However,the role of CircRNA in autoimmune hepatitis remains unclear. OBJECTIVE:To investigate the relationship between CircRNA(CircRNA)and concanavalin A induced liver injury in mice with autoimmune hepatitis. METHODS:Bioinformatics analysis was performed on CircRNA profiles selected by previous microarray technology,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,so as to explore the potential biological functions of these differentially expressed genes.Twelve C57BL/6 mice were randomized into normal group and model group(n=6 per group).Autoimmune hepatitis model was established by tail vein injection of concanavalin A in the model group.Mice were killed at 12 hours after modeling to extract mouse liver and peripheral blood.The expression levels of CircRNAs were verified by qRT-PCR.Serum alanine aminotransferase and aspartate aminotransferase levels were detected by colorimetric method.The levels of oxidative stress indexes malondialdehyde and nitric oxide in mouse liver were detected by microplate method.The correlation between oxidative stress level and liver injury index was analyzed. RESULTS AND CONCLUSION:The results of GO analysis showed that the target genes with up-regulated CircRNAs expression were mainly involved in the biological processes of SNARE complex assembly regulation(P=0.004),their molecular functions were mainly metal ion binding(P=0.000 29),and the cell components were mainly enriched in CORVET complex(P=0.075).The biological processes involved in the down-regulated circRNAs target genes were mainly"negative regulation of pancreatic secretion"(P=0.000 42),the molecular functions were mainly"transcriptional activator activity"(P=0.025),and the cell components were mainly enriched in"extracellular components"(P=0.006).KEGG results showed that the target genes with up-regulated CircRNAs expression were mainly enriched in the"base excision-repair"signaling pathways(P=0.026).Compared with the normal group,serum alanine aminotransferase and aspartate aminotransferase levels and the levels of malondialdehyde and nitric oxide in mouse liver in the model group were significantly increased(P＜0.01).Compared with the normal group,the expression of two selected CircRNAs(mmu-circ-0001520 and mmu-circ-0001577)was increased in the model group(P＜0.05).Spearman correlation analysis showed that the expression of mmu-circ-0001520 and mmu-circ-0001577 was positively correlated with alanine aminotransferase,aspartate aminotransferase,malondialdehyde and nitric oxide.To conclude,the differential expression of CircRNAs is correlated with liver injury in autoimmune hepatitis mice.mmu-circ-0001520 and mmu-circ-0001577 are expected to be diagnostic biomarkers and therapeutic targets for autoimmune hepatitis.
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@#Oral submucous fibrosis (OSF) is one of the most common precancerous lesions of the oral mucosa, and its pathogenesis has not been fully elucidated. Small noncoding RNAs (SncRNAs), a class of RNA molecules that do not code for proteins, have been widely reported to be involved in the regulation of a variety of human diseases. An increasing number of studies have shown that a variety of SncRNAs play important roles in the pathogenesis of OSF. Current studies have shown that microRNAs (miRNAs) are involved in OSF disease progression by regulating the expression of related transcription factors and genes or epithelial mesenchymal transformation to regulate the activation of fibroblasts (FBs). Long noncoding RNAs (lncRNAs) that transform growth factor-β/suppressor of mothers against decapentaplegic (TGF-β/Smad) signaling pathways or interact with miRNAs are involved in the development of OSF. Circular RNAs (circRNAs) play a role in OSF by interacting with miRNAs. tRNA-derived small RNAs (tsRNAs) are involved in the progression of various fibrotic diseases, but their specific mechanism of action in OSF still needs to be further explored. In the future, it is still necessary to focus on the targets of SncRNAs mediating OSF progression and explore their function and molecular mechanism in OSF to provide new ideas for the diagnosis and treatment of OSF.
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Many circular RNAs(circRNAs)have been discovered and identified as noncoding RNA in various organisms in a specie-, tissue-, disease-and developmental stage-specific manner, and have been demonstrated to play essential roles in myriad life processes, such as embryo and tissue development, aging, insulin secretion, vascular disease and cancer.The normal development of lung morphology, structure and function is the physiological basis of breath.Accumulating evidences have been demonstrated that circRNAs might be involved in lung development and play important roles in lung development and related diseases like bronchopulmonary dysplasia(BPD).This review will summarize the biological functions of circRNAs and focus particularly on the potential implications of circRNAs in lung development and BPD.
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Environmental exposure is an important factor in the occurrence and development of various lung diseases. Circular RNAs (circRNAs) are a class of noncoding RNA molecules, which are widely expressed in eukaryotes, and have been proved to play an important role in the occurrence and progression of a variety of human diseases. Studies have shown that circRNAs are closely related to various lung diseases, and have been used as diagnostic and prognostic biomarkers and therapeutic targets of some lung diseases. This review briefly described the physiological functions and molecular mechanisms of circRNAs, and summarized the regulatory mechanisms of circRNAs in lung diseases caused by environmental exposure, in order to provide new ideas for the research and application in related fields in the future.
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With the development of high-throughput sequencing technology, circular RNAs (circRNAs) have gradually become a hotspot in the research on non-coding RNA. CircRNAs are produced by the covalent circularization of a downstream 3' splice donor and an upstream 5' splice acceptor through backsplicing, and they are pervasive in eukaryotic cells. CircRNAs used to be considered byproducts of false splicing, whereas an explosion of related studies in recent years has disproved this misconception. Compared with the rich studies of circRNAs in animals, the study of circRNAs in plants is still in its infancy. In this review, we introduced the discovery of plant circRNAs, the discovery of plant circRNAs, the circularization feature, expression specificity, conservation, and stability of plant circRNAs and expounded the identification tools, main types, and biogenesis mechanisms of circRNAs. Furthermore, we summarized the potential roles of plant circRNAs as microRNA (miRNA) sponges and translation templates and in response to biotic/abiotic stress, and briefed the degradation and localization of plant circRNAs. Finally, we discussed the challenges and proposed the future directions in the research on plant circRNAs.
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Animaux , microARN/métabolisme , Biogenèse des organelles , Plantes/métabolisme , Biosynthèse des protéines/physiologie , ARN circulaire/métabolisme , ARN des plantes/métabolisme , Recherche/tendances , Stress physiologique/génétiqueRésumé
@#Circular RNAs(circRNAs)comprise a novel class of non-coding RNAs that are found to be highly abundant in eukaryotic cells and have implicated in various cellular functions such as cell proliferation, differentiation, and apoptosis. Recent advances have suggested that dysregulated circRNAs play a critical role in the pathogenesis of several proliferative retinal diseases including proliferative vitreous retinopathy, diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and corneal neovascularization. Here, we review current knowledge about circRNAs and summarize new insights into potential functions of some aberrantly expressed circRNAs and possible future directions in ocular proliferative diseases.
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Tumor immunotherapy is a new therapy which developed in recent years, it has greatly changed the therapeutic schedules and brought new options for patients. However, not all patients can have obvious therapeutic effects after using immunotherapy. So selecting more suitable patients and raising immunotherapy effect are worthy to discuss. With the research of circular RNAs (circRNAs), circRNAs have been found that they not only play a significant role in the field of tumor markers, tumor progression and prognosis, but also can abnormally express in a variety of tumors and affect tumor immunity. Therefore, the circRNAs expression may not only can be used as a supplementary method for selecting patients, but also can be used to predict the efficacy of tumor immunotherapy. In this article, we summarize current knowledge on circRNAs abnormally expressed in many cancers, especially lung cancer which can affect tumor immunity, and discuss its potential effects in tumor immunotherapy, and we hope to provide more references for the clinical practice of circRNAs. .
Sujets)
Humains , Marqueurs biologiques tumoraux , Immunothérapie , Tumeurs du poumon/thérapie , Pronostic , ARN circulaireRésumé
Background: Circular RNAs (circRNAs) is correlated with the development and progression of malignant tumor. Recent studies have shown the potentials of some circRNAs in the early diagnosis, screening of therapeutic targets and prognostic judgment of gastric cancer. Aims: To investigate the serum circNRIP1 expression and its clinical significance in the diagnosis, treatment and prediction of prognosis of gastric cancer. Methods: A total of 76 gastric cancer patients diagnosed by pathology from September 2016 to September 2019 at Dujiangyan People's Hospital were enrolled, and 63 healthy individuals were served as controls. Serum circNRIP1 expression was detected by real time fluorescent quantitative PCR, and its correlation with clinicopathological features was analyzed. ROC curve was used to analyze the diagnostic efficiency. Results: Serum circNRIP1 expression in gastric cancer group was significantly higher than that in healthy control group (P<0.01). The circNRIP1 expression in gastric cancer patients was significantly correlated with the differentiation of tumor cells, depth of infiltration, lymph node metastasis and TNM stage (P<0.05). Serum circNRIP1 expression in gastric cancer patients after operative treatment was significantly lower than that before treatment (P<0.05). After 2 years follow-up, serum circNRIP1 expression in survival group was significantly lower than that in death group (P<0.05). ROC curve analysis showed that the sensitivity of serum circNRIP1 expression for gastric cancer was 88.9%, the specificity was 88.2%, and AUC was 0.876. Conclusions: Detecting serum circNRIP1 expression has significant value in the early diagnosis and evaluation of treatment and prediction of prognosis of gastric cancer.
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【Objective】 To investigate the effect of transfusion-transmitted Zika virus (ZIKV) on the expression of non-coding circular RNA (hsa_circ_0001613) and the role of hsa_circ_0001613 in Zika virus replication. 【Methods】 Human adenocarcinomic alveolar basal epithelial cells (A549) were seeded on a 12-well plate at 1.8×105/ well and infected with ZIKV at 0.05 MOI. The Total RNAs were isolated every day for 5 days after infection, and the relative expression level of hsa_circ_0001613 was detected by qRT-PCR. In addition, 10nM siRNA-hsa_circ_0001613 was transfected into 2×105/ well A549 cells to specifically knock down the expression level of hsa_circ_0001613. 24h later, the cells were infected with ZIKV (MOI=0.05). Total RNAs were isolated at day 1-5 post-infection, proteins were extracted 96h post-infection. ZIKV replication, relative host antiviral gene expression, and interferon stimulated response element (ISRE) activity were tested using qRT-PCR, western blot and dual luciferase assay, respectively. 【Results】 The relative expression of hsa_circ_0001613 decreased significantly after 1-5 days of ZIKV infection. Knockdown of hsa_circ_0001613 inhibited ZIKV replication. Meanwhile, hsa_circ_0001613 knockdown significantly upregulated IFN-α/β and its downstream interferon-stimulated genes (ISGs) expression, also increased ISRE activity. 【Conclusion】 ZIKV infection significantly suppressed hsa_circ_0001613 expression in A4549 cells. Preliminary study indicated that hsa_circ_0001613 knockdown inhibited ZIKV replication possibly through activating type-Ⅰ IFN signaling pathway as showed by increased ISGs expression and ISRE activity.
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@#With the continuous development of maxillary sinus floor elevation technology, the osteogenesis mechanism of maxillary sinus floor elevation has always been a concern of scholars. The membrane of the maxillary sinus is an indispensable physiological structure in the process of space osteogenesis under the sinus floor after elevation of the sinus floor. In recent years, the role of the maxillary sinus floor mucosa in sinus floor space osteogenesis has been a research hotspot. Recent studies have found that the maxillary sinus floor membrane plays a role as a natural biological barrier membrane in the process of sinus floor space osteogenesis after maxillary sinus floor elevation; in addition, it has the ability to undergo osteogenesis. It has also been found that maxillary sinus membrane stem cells (MSMSCs) derived from the maxillary sinus floor membrane have characteristics of mesenchymal stem cells, which can differentiate into osteoblasts and participate in sinus floor space osteogenesis after maxillary sinus floor elevation. New studies have also found that small RNAs such as microRNAs, long noncoding RNAs and circular RNAs can regulate the osteogenic differentiation of MSMSCs, which may be important biological targets for promoting osteogenesis in the sinus floor space. In this paper, the relationship between the maxillary sinus floor mucosa and bone formation after maxillary sinus floor elevation, the barrier and osteogenic function of the maxillary sinus floor mucosa, the sources of osteoblasts involved in osteogenesis of the sinus floor space, and the molecular regulatory mechanisms of stem cells derived from maxillary sinus mucosa will be elucidated step by step.
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Objective: To investigate the expression of circular RNA circSP3 (hsa-circ-0002642) in hepatocellular carcinoma (HCC) and its effect on proliferation and migration of HCC cells. Methods: The tumor tissue and the adjacent paratumor tissue samples were collected from 42 HCC patients who underwent surgery from Jun. 2017 to Dec. 2018 in Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University. The expression of circSP3 in the samples was detected by real-time quantitative PCR, and the relationship between circSP3 expression in the tumor tissues and clinicopathological parameters of the patients was analyzed. Human HCC cell lines (Hep-3B, Huh7, SMMC-7721 and Bel-7402) and human normal liver cell line (HL-7702) culturion, and the expression of circSP3 was detected. After circSP3 overexpression and interference plasmids transfection into Hep-3B and Huh7 cells, the cell proliferation was detected by cell counting kit-8 (CCK-8) method, the invasion and migration abilities were detected by Transwell assay, and expression levels of epithelial-mesenchymal transformation (EMT)-associated markers (vimentin and E-cadherin) were determined by Western blotting. Results: The expression of circSP3 of tumor tissues was significantly higher than that of the paratumor tissues in the HCC patients (P < 0.01), and the expression of circSP3 was positively correlated with the tumor maximum diameter and clinical TNM stage (both P < 0.05). The expression levels of circSP3 in the 4 HCC cell lines were significantly higher than that in the normal liver cell lines (all P < 0.01). Overexpression of circSP3 could significantly promote proliferation, invasion and migration of HCC cells (P < 0.05, P < 0.01), while interference circSP3 expression could significantly inhibit the proliferation, invasion and migration (P < 0.05, P < 0.01). The expression of vimentin was significantly higher in circSP3-overexpressed cells than that in control cells (P < 0.05), while it was significantly lower in circSP3-interfered cells than that in control cells (P < 0.05). The expression of E-cadherin was significantly lower in circSP3-overexpressed cells than that in control cells (P < 0.01), while it was significantly higher in circSP3-interfered cells than that in control cells (P < 0.01). Conclusion: The abnormal expression of circSP3 is positively correlated with tumor size and TNM stage of HCC, and determining its expression is helpful to evaluate the severity and prognosis of HCC. CircSP3 can promote the proliferation of HCC cells, and may promote the migration and invasion by promoting the EMT process.
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Objective@#Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.@*Data sources@#The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science.@*Study selection@#The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.@*Results@#CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5＇ and 3＇ ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases.@*Conclusions@#Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.
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Circular RNAs (circRNAs) are currently classed as non-coding RNAs that, unlike the better known canonical linear RNAs, form a covalently closed continuous loop without 5′ or 3′ polarities. With the development of high throughput sequencing technology, a large number of circRNAs have been discovered in many species. More importantly, growing evidence suggests that circRNAs are abundant, evolutionally conserved, and relatively stable in cells and tissues. Strikingly, recent studies have discovered that circRNAs can serve as microRNA sponges, interact with RNA-binding protein, and regulate gene transcription, as well as protein translation. Osteoarthritis (OA) is the most common chronic degenerative joint disease. CircRNAs are differentially expressed in OA cartilage. Moreover, some circRNAs are involved in multiple pathological processes during OA, mainly extracellular matrix degradation, inflammation, and apoptosis. In this review, we briefly delineate the biogenesis, characteristics, and biofunctions of circRNAs, and then, focus on the role of circRNAs in the occurrence and progression OA.
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Apoptose , Cartilage , Cartilage articulaire , Matrice extracellulaire , Inflammation , Maladies articulaires , microARN , Arthrose , Processus pathologiques , Porifera , Biosynthèse des protéines , ARN , ARN non traduit , Protéines de liaison à l'ARNRésumé
Circular RNA (circRNA) is a novel type of endogenous non-coding RNA (ncRNA), which mainly derives from exons or introns, and is generated by back splicing or lariat introns. Different from linear RNAs, circRNAs are stable and abundant in expression, and also show tissue- or developmental stage-specific expression. More and more evidence has indicated that circRNAs may be abnormal in expression in many diseases, especially in tumor cells, which plays a role through regulating the expressions of key genes. A large number of circRNAs are present in saliva, exosomes and the blood, and they may become biomarkers for diagnosis and prognostic evaluation of cancer.
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AIM:To determine circular RNA (circRNA) profiles in the diabetic mouse myocardium , and to investigate the effect of circRNA_000203 on fibrotic phenotypes in cardiac fibroblasts .METHODS:Masson trichrome stai-ning was performed on the myocardium of the diabetic db /db mice and the non diabetic db/m control mice .circRNA ex-pression profile in the diabetic myocardium was detected by circRNAs microarray .The expression of circRNA_000203 was determined by real time fluorescence quantitative PCR ( RT-qPCR ) .Recombinant circRNA_000203 adenovirus was pre-pared for enforced the expression of circRNA_000203 in mouse cardiac fibroblasts.The expression of Col1a2, Col3a1andα-SMA was determined in circRNA_000203-modified cardiac fibroblasts , respectively .RESULTS:Masson trichrome stai-ning showed that fibrosis was increased in the diabetic mouse myocardium .The results of circRNA array detection revealed that circRNAs were dysregulated in the diabetic myocardium .circRNA_000203 was up-regulated in the diabetic myocardi-um.Significant over-expression of circRNA_000203 was achieved in the cardiac fibroblasts after infection with the recombi-nant circRNA_000203 adenovirus.The mRNA and protein expression of Col1a2, Col3a1 and α-SMA was significantly in-creased in the cardiac fibroblasts with over-expression of circRNA_000203.CONCLUSION:circRNA_000203 is up-regu-lated in the diabetic mouse myocardium .It has pro-fibrotic effect on the cardiac fibroblasts .