Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mech...BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.展开更多
BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,thi...BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,this mechanism has no evidence yet.This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells.The chosen approach is loss of signal and functional gain.AIM To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role.Results provide reference for other researchers to develop targeted treatment plans.METHODS The gene expression omnibus(GEO)database can be used to obtain the microarray dataset GSE83521.Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples.Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples.GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA(pcDNA)-hsa_ircRNA_102415.Multiple detection methods,such as Transwell and cell counting kit 8,were used to evaluate cellular physiological activities,including cell invasion and proliferation.The relationship between Wnt family members 2B,microRNA(miR)-4529-5p,etc.,including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed.Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415.RESULTS GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues.hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells,suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p.miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions.CONCLUSION miR-4529-5p was used to successfully activate the potential of WNT2B,clarify the role of hsa_circRNA_102415 in GC cells,and provide reference for other researchers to develop targeted treatment plans.展开更多
Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC...Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.展开更多
Circular RNAs(circRNAs)are a distinct type of nonlinear and noncoding RNAs endogenously expressed by pre-mRNA back-splicing and crucial in transcriptional and posttranscriptional regulation.CircRNAs can regulate cellu...Circular RNAs(circRNAs)are a distinct type of nonlinear and noncoding RNAs endogenously expressed by pre-mRNA back-splicing and crucial in transcriptional and posttranscriptional regulation.CircRNAs can regulate cellular and molecular pathways through various mechanisms,such as microRNA sponging.Numerous studies have indicated the regulatory roles of circRNAs in the osteogenic differentiation of stem cells(SCs)isolated from different sources.Dental tissue-derived mesenchymal SCs(MSCs)have received considerable attention in artificial bone engineering,in which SCs are used to manufacture functional bone tissues to repair bone defects.Recently,studies have reported the regulatory roles of circRNAs in the osteogenic differentiation of dental-derived MSCs,such as apical papillae,dental pulp,and dental follicle SCs.This review aimed to discuss the findings of studies evaluating the contribution of circRNAs to the osteogenic differentiation of dental-derived MSCs.展开更多
The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory netwo...The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory network plays a crucial role in CSC properties.Regulatory non-coding RNA(ncRNA),including microRNAs,long noncoding RNAs,and circular RNAs,have an important influence on cell physiopathology.They modulate cells by regulating gene expression in different ways.This review discusses the basic characteristics and the physiological functions of colorectal cancer(CRC)stem cells.Elucidation of these ncRNAs will help us understand the pathological mechanism of CRC progression,and they could become a new target for cancer treatment.展开更多
BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognos...BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.展开更多
Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates ...Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates intrinsic exonuclease resistance.Current circularization strategies face three principal limitations:chemical methods produce non-native 2',5'-phosphodiester bonds;ribozyme-mediated approaches are restricted to RNA fragments shorter than 500 nucleotides;the Anabaena Group I intron system retains immunogenic exon sequences.In contrast,the self-splicing Group I intron ribozyme from Tetrahymena enables precisely controlled circularization through autonomous structural rearrangement,yielding exonfree constructs.Through optimized purification protocols,historical scalability challenges are systematically addressed.This Perspective establishes the mechanistic rationale and therapeutic superiority of this engineered RNA circularization platform.展开更多
Colorectal cancer(CRC)is a common and deadly malignancy worldwide,causing high morbidity and mortality rates.Chemoresistance continues to be the major barrier to the effective treatment of CRC.Circular RNA(circRNA),a ...Colorectal cancer(CRC)is a common and deadly malignancy worldwide,causing high morbidity and mortality rates.Chemoresistance continues to be the major barrier to the effective treatment of CRC.Circular RNA(circRNA),a recently identified class of non-coding RNA,has become an emerging focus in CRC research due to its abundant presence and stability in extracellular vesicles(EVs).The circRNA of EVs(EVs-circRNA)is closely associated with CRC progression and plays a pivotal role in chemoresistance mechanisms.This paper investigates the circRNA mechanism underlying different chemoresistance scenarios in CRC and explores the dual role of EVs-circRNA in mediating chemotherapy resistance.Furthermore,EVs-circRNA,a non-invasive biomarker for liquid biopsies,holds significant promise in clinical applications,ranging from early CRC diagnosis to monitoring disease progression and assessing prognosis.These studies provide a new perspective for uncovering CRC pathogenesis and lay the foundation for precision therapy and personalized treatment strategies for CRC.In the future,therapeutic strategies targeting EVs-circRNAs are anticipated to revolutionize CRC treatment,leading to improved therapeutic outcomes and enhanced quality of life for patients.展开更多
Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Neverthel...Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Nevertheless, few studies have focused on the underlying mechanisms of LNM. In the current study, we aimed to investigate the potential role of exosomal circRNAs that contribute to LNM in PTC. We identified 9 000 differentially expressed exosomal circRNAs in PTC patients with LNM, including 684 upregulated and 2 193 downregulated circRNAs. Functional enrichment analysis revealed that these differentially expressed circRNAs were primarily involved in a variety of molecular and signaling pathways correlated with PTC progression and LNM. Through bioinformatics analysis, we identified 14 circRNA-miRNA-mRNA networks related to LNM-associated signaling pathways in PTC. Moreover, both circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for their potential involvement in PTC with LNM. Additionally, we identified four upregulated circRNA-related hub genes and eight hub genes correlated with downregulated circRNAs, some of which were validated as being potentially involved in LNM in PTC. Collectively, our findings provide a novel framework for an in-depth investigation of the function of dysregulated exosomal circRNAs and their potential as biomarkers in PTC patients with LNM.展开更多
Circular RNAs(circRNAs)are formed by splicing of precursor RNAs and covalently linked at the 5′and 3′ends.Dysregulated circRNAs are closely related to the epithelial-mesenchymal transition(EMT)of gastrointestinal ma...Circular RNAs(circRNAs)are formed by splicing of precursor RNAs and covalently linked at the 5′and 3′ends.Dysregulated circRNAs are closely related to the epithelial-mesenchymal transition(EMT)of gastrointestinal malignancies.CircRNAs,including circRNA_0008717,circGOT1,circ-DOCK5,circVPS33B,circPVT1,circMET,circ-OXCT1,circ_67835,circRTN4,circ_0087502,circFNDC38,circ_PTEN1,circPGPEP1,and circ-E-Cad are involved in the EMT process of gastrointestinal malignancies through a variety of mechanisms,such as regulating EMT-inducing transcription factors,signaling pathways,and tumor microenvironments.Gastrointestinal(GI)malignancies are common malignant tumors worldwide,and the heterogeneity and easy metastasis of gastrointestinal malignancies limit the effectiveness of medical treatments.Therefore,investigating the molecular mechanisms involved in the pathogenesis of gastrointestinal malignancies is essential for clinical treatment.This article summarizes the biological roles and molecular mechanism of circRNAs in EMT of gastrointestinal malignancies,providing a theoretical basis for applying EMT-related circRNAs in targeted therapy.展开更多
BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship betwe...BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship between EMVI and expression of the circular RNA hsa_circ_0097977 in orthotopic GC mouse models.METHODS A retrospective analysis was conducted in addition to a preclinical animal study,involving 13 GC patients and 24 orthotopic GC mouse models,respectively.EMVI was assessed using axial T2-weighted fat suppression sequences on a 9.4T magnetic resonance imaging(MRI)with histopathological confirmation as the gold standard for EMVI.The impact of hsa_circ_0097977 on EMVI and GC cell function was evaluated.Statistical analyses comprised consistency,area under the curve analysis,correlation,χ^(2)/Fisher exact,and Mann-Whitney U/t-tests,with significance set at P<0.05.RESULTS EMVI was accurately detected using 9.4T MRI in orthotopic mouse models with an area under the curve of 0.843(sensitivity 78.6%,specificity 90.0%).MRI detected EMVI was the only imaging factor associated with distant metastasis(P=0.04).Furthermore,knockdown of hsa_circ_0097977 was the only factor associated with EMVI(P=0.043,0.038)and led to reduced invasion and increased apoptosis in GC cells.CONCLUSION EMVI,a risk factor for distant metastasis in GC,is detectable by 9.4T MRI and regulated by hsa_circ_0097977,making it a potential therapeutic target.展开更多
Background:Sunitinib resistance is a major challenge in advanced renal cell carcinoma(RCC).Clinically,elucidating the underlying mechanisms and developing practical countermeasures for sunitinib resistance in RCC is d...Background:Sunitinib resistance is a major challenge in advanced renal cell carcinoma(RCC).Clinically,elucidating the underlying mechanisms and developing practical countermeasures for sunitinib resistance in RCC is desirable.In previous studies,we found that circAGAP1 expression was significantly upregulated in clear cell RCC(ccRCC)and was strongly associated with poor prognosis.However,the role of circAGAP1 in sunitinib resistance in ccRCC remains unclear.Methods:We used public databases for bioinformatics analysis to identify the binding targets of circAGAP1.Additionally,the effects of circAGAP1 on the proliferation,clonogenesis,apoptosis,and migration of ccRCC cells were analyzed using quantitative real-time PCR,cell counting kit-8 assays,migration and apoptosis assays,and colony formation assays.Furthermore,RNA immunoprecipitation,dual-luciferase reporter,and fluorescence in situ hybridization assays were used to explore the molecular mechanism.Results:In this study,circAGAP1 exhibited higher expression in sunitinib-sensitive ccRCC cells and inhibited the clonogenesis,proliferation,and migration of ccRCC cells after sunitinib treatment.Mechanical studies revealed that circAGAP1 regulated the expression of sunitinib target platelet-derived growth factor receptor by acting as a microRNA sponge that suppresses miR-149-5p,miR-455-5p,and miR-15a-5p simultaneously.Overexpression of these three miRNAs reversed circAGAP1-mediated sunitinib sensitivity in ccRCC.Conclusions:In summary,our findings indicate that circAGAP1 may serve as a promising biomarker to predict sunitinib sensibility and a therapeutic target in ccRCC.展开更多
Circular RNAs(circRNAs),a new star of noncoding RNAs,are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome.Most circRNAs are conserved throughout species and fre-...Circular RNAs(circRNAs),a new star of noncoding RNAs,are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome.Most circRNAs are conserved throughout species and fre-quently show stage-specific expression during various stages of tissue develop-ment.CircRNAs were a mystery discovery,as they were initially believed to be a product of splicing errors;however,subsequent research has shown that ci-rcRNAs can perform various functions and help in the regulation of splicing and transcription,including playing a role as microRNA(miRNA)sponges.With the application of high throughput next-generation technologies,circRNA hotspots were discovered.There are emerging indications that explain the association of circRNAs with human diseases,like cancers,developmental disorders,and in-flammation,and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases,including cancer.After the discoveries of miRNAs and long noncoding RNAs,circRNAs are now acting as a novel re-search entity of interest in the field of RNA disease biology.In this review,we aim to focus on major updates on the biogeny and metabolism of circRNAs,along with their possible/established roles in major human diseases.展开更多
Bone is a connective tissue that has important functions in the human body.Cells and the extracellular matrix(ECM)are key components of bone and are closely related to bone-related diseases.However,the outcomes of con...Bone is a connective tissue that has important functions in the human body.Cells and the extracellular matrix(ECM)are key components of bone and are closely related to bone-related diseases.However,the outcomes of conventional treatments for bone-related diseases are not promising,and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy.Circular RNAs(circRNAs)are single-stranded RNAs that form closed circular structures without a 5’cap or 3’tail and polycyclic adenylate tails.Due to their high stability,circRNAs have the potential to be typical biomarkers.Accumulating evidence suggests that circRNAs are involved in bone-related diseases,including osteoarthritis,osteoporosis,osteosarcoma,multiple myeloma,intervertebral disc degeneration,and rheumatoid arthritis.Herein,we summarize the recent research progress on the characteristics and functions of circRNAs,and highlight the regulatory mechanism of circRNAs in bone-related diseases.展开更多
Advancing knowledge of the transcriptome has revealed that circular RNAs(circRNAs)are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles.More interesting is the accumulati...Advancing knowledge of the transcriptome has revealed that circular RNAs(circRNAs)are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles.More interesting is the accumulating evidence which demonstrates the implication of circRNAs in diseases,especially cancers.This revelation has helped to form the rationale for many studies exploring their utility as clinical biomarkers.CircRNAs are highly stable due to their unique structures,exhibit some tissue specificity,and are enriched in exosomes,which facilitate their detection in a range of body fluids.These properties make circRNAs ideal candidates for biomarker development in many diseases.This review will outline the discovery,biogenesis,and proposed functions of circRNAs.展开更多
Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate i...Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate in the survival and differentiation of multiple nerve cells,and may even promote the recovery of neurological function after stroke.However,their role in the inflammatory response after spinal cord injury remains unclear.In the present study,we established a mouse model of T9 spinal cord injury using the modified Allen’s impact method,and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury.Of these,the expression levels of circPrkcsh were significantly different between injured and sham-treated mice.We then treated astrocytes with tumor necrosis factor-αin vitro to simulate the inflammatory response after spinal cord injury.Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells.We also found that circPrkcsh regulated the expression of the inflammationrelated gene Ccl2.Furthermore,in tumor necrosis factor-α-treated astrocytes,circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression,and reduced the secretion of inflammatory cytokines in vitro.These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs.Furthermore,circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression,which might provide a new potential therapy for SCI.The study was approved by the Animal Ethics Committee of Shandong University of China(approval No.KYLL-20170303)on March 3,2017.展开更多
Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ R...Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ RNAs) have been reported to contribute to the pathogenesis of AD. We found an age-dependent elevation of mi R-138 in APP/PS1(presenilin-1) mice. Mi R-138 inhibited the expression of ADAM10 [a disintegrin and metalloproteinase domain-containing protein 10], promoted amyloid beta(Ab) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice. Overexpression of sirtuin 1(Sirt1), a target of mi R-138, ameliorated the mi R-138-induced inhibition of ADAM10 and elevation of Ab in vitro. The circ RNA HDAC9(circ HDAC9) was predicted to contain a mi R-138 binding site in several databases. Its expression was inversely correlated with mi R-138 in both Ab-oligomertreated N2 a cells and APP/PS1 mice, and it co-localized with mi R-138 in the cytoplasm of N2 a cells. Circ HDAC9 acted as a mi R-138 sponge, decreasing mi R-138 expression, and reversing the Sirt1 suppression and excessive Ab production induced by mi R-138 in vitro. Moreover,circ HDAC9 was decreased in the serum of both AD patients and individuals with mild cognitive impairment.These results suggest that the circ HDAC9/mi R-138/Sirt1 pathway mediates synaptic function and APP processing in AD, providing a potential therapeutic target for its treatment.展开更多
As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of...As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.展开更多
BACKGROUND Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level,circular RNAs(circRNAs)participate in the pathogenesis of ...BACKGROUND Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level,circular RNAs(circRNAs)participate in the pathogenesis of a variety of diseases and are considered ideal biomarkers of human disease.AIM To examine the expression of circRNA_103516 in inflammatory bowel disease(IBD)and its associations with clinical phenotypes and inflammatory cytokines.METHODS Peripheral blood mononuclear cells(PBMCs)were obtained from patients with IBD,healthy controls(HCs),and patient controls(PCs).Expression of circRNA_103516 and hsa-miR-19b-1-5p was assessed by quantitative reverse transcription-polymerase chain reaction.Crohn's disease activity index(CDAI),Mayo score,C-reactive protein(CRP)level,and erythrocyte sedimentation rate(ESR)were measured.To assess the inflammatory cytokines tumour necrosis factorα(TNF-α),interferon-γ(IFN-γ),and interleukin-10(IL-10),blood samples were analysed by flow cytometry.RESULTS Ninety Crohn’s disease(CD)and 90 ulcerative colitis(UC)patients,80 HCs,and 35 PCs were included in the study.CircRNA_103516 was upregulated in CD and UC patients compared with HCs and PCs(P<0.05).The area under the curve of circRNA_103516 for diagnosing CD and UC was 0.790 and 0.687,respectively.In addition,circRNA_103516 levels were increased in active CD and UC compared with remittent groups(P=0.027,P=0.045).Furthermore,in CD,circRNA_103516 correlated positively with CDAI(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),and IFN-γ(P<0.001)and negatively correlated with IL-10(P=0.006).In UC patients,circRNA_103516 correlated with Mayo score(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),IFN-γ(P=0.011),and IL-10(P=0.002).Additionally,circRNA_103516 correlated positively with stricturing(P=0.018)and penetrating(P=0.031)behaviour.Moreover,hsamiR-19b-1-5p correlated negatively with circRNA_103516 in CD.CONCLUSION CircRNA_103516 levels in PBMCs can be considered an ideal candidate biomarker for diagnosing IBD.Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LQ23H020004The Medical and Health Research Project of Zhejiang province,No.2024KY983Basic Medical Health Technology Project of Wenzhou Science and Technology Bureau,No.Y20210818 and No.Y20210140.
文摘BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.
文摘BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,this mechanism has no evidence yet.This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells.The chosen approach is loss of signal and functional gain.AIM To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role.Results provide reference for other researchers to develop targeted treatment plans.METHODS The gene expression omnibus(GEO)database can be used to obtain the microarray dataset GSE83521.Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples.Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples.GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA(pcDNA)-hsa_ircRNA_102415.Multiple detection methods,such as Transwell and cell counting kit 8,were used to evaluate cellular physiological activities,including cell invasion and proliferation.The relationship between Wnt family members 2B,microRNA(miR)-4529-5p,etc.,including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed.Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415.RESULTS GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues.hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells,suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p.miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions.CONCLUSION miR-4529-5p was used to successfully activate the potential of WNT2B,clarify the role of hsa_circRNA_102415 in GC cells,and provide reference for other researchers to develop targeted treatment plans.
文摘Colorectal cancer(CRC) is the third most commonly diagnosed cancer in the world and the fourth principal cause of cancer deaths worldwide. Currently, there is a lack of low cost and noninvasive screening tests for CRC, becoming a serious health problem. In this context, a potential biomarker for the early detection of CRC has recently gained attention. Circular RNAs(circ RNA), a re-discovered, abundant RNA specie, is a type of noncoding covalent closed RNAs formed from both exonic and intronic sequences. These circular molecules are widely expressed in cells, exceeding the abundance of the traditional linear m RNA transcript. They can regulate gene expression, acting as real sponges for mi RNAs and also regulate alternative splicing or act as transcriptional factors and inclusive encoding for proteins. However, little is known about circ RNA and its relationship with CRC. In this review, we focus on the biogenesis, function and role of these circ RNAs in relation to CRC, including their potential as a new biomarker.
文摘Circular RNAs(circRNAs)are a distinct type of nonlinear and noncoding RNAs endogenously expressed by pre-mRNA back-splicing and crucial in transcriptional and posttranscriptional regulation.CircRNAs can regulate cellular and molecular pathways through various mechanisms,such as microRNA sponging.Numerous studies have indicated the regulatory roles of circRNAs in the osteogenic differentiation of stem cells(SCs)isolated from different sources.Dental tissue-derived mesenchymal SCs(MSCs)have received considerable attention in artificial bone engineering,in which SCs are used to manufacture functional bone tissues to repair bone defects.Recently,studies have reported the regulatory roles of circRNAs in the osteogenic differentiation of dental-derived MSCs,such as apical papillae,dental pulp,and dental follicle SCs.This review aimed to discuss the findings of studies evaluating the contribution of circRNAs to the osteogenic differentiation of dental-derived MSCs.
文摘The properties of cancer stem cells(CSCs),such as self-renewal,drug resistance,and metastasis,have been indicated to be responsible for the poor prognosis of patients with colon cancers.The epigenetic regulatory network plays a crucial role in CSC properties.Regulatory non-coding RNA(ncRNA),including microRNAs,long noncoding RNAs,and circular RNAs,have an important influence on cell physiopathology.They modulate cells by regulating gene expression in different ways.This review discusses the basic characteristics and the physiological functions of colorectal cancer(CRC)stem cells.Elucidation of these ncRNAs will help us understand the pathological mechanism of CRC progression,and they could become a new target for cancer treatment.
基金supported by grants from the municipal Natural Science Foundation of Shanghai Scientific Committee of China(22ZR1451000 to TL)the peak supporting clinical discipline of Shanghai Health Bureau(2023ZDFC0104 to TL)+3 种基金the key clinical discipline of Shanghai Pudong Health Bureau(PWZxk2022-17 to TL)the clinical peak discipline of Shanghai Pudong Heath Bureau(PWYgf2021-03)the top-notch innovative medical talents of Shanghai Pudong Health Bureau(2025PDWSYCBJ-03 to TL)the leading medical talent project of Shanghai Pudong Heath Bureau(PWR12020-07 to LS)。
文摘BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.
基金supported by the National Key Research&Development Program of China(Nos.2021YFC2302400,2021YFA1201000,2023YFC2606004)the Fundamental Research Funds for the Central Universities(No.2022CX01013)。
文摘Linear mRNA vaccines are constrained by exonuclease susceptibility and instability,leading to compromised antigen expression.Circular RNA(circRNA) lacking canonical 5' and 3' untranslated regions demonstrates intrinsic exonuclease resistance.Current circularization strategies face three principal limitations:chemical methods produce non-native 2',5'-phosphodiester bonds;ribozyme-mediated approaches are restricted to RNA fragments shorter than 500 nucleotides;the Anabaena Group I intron system retains immunogenic exon sequences.In contrast,the self-splicing Group I intron ribozyme from Tetrahymena enables precisely controlled circularization through autonomous structural rearrangement,yielding exonfree constructs.Through optimized purification protocols,historical scalability challenges are systematically addressed.This Perspective establishes the mechanistic rationale and therapeutic superiority of this engineered RNA circularization platform.
基金Supported by Open Project of National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,No.NCRCOP2023007.
文摘Colorectal cancer(CRC)is a common and deadly malignancy worldwide,causing high morbidity and mortality rates.Chemoresistance continues to be the major barrier to the effective treatment of CRC.Circular RNA(circRNA),a recently identified class of non-coding RNA,has become an emerging focus in CRC research due to its abundant presence and stability in extracellular vesicles(EVs).The circRNA of EVs(EVs-circRNA)is closely associated with CRC progression and plays a pivotal role in chemoresistance mechanisms.This paper investigates the circRNA mechanism underlying different chemoresistance scenarios in CRC and explores the dual role of EVs-circRNA in mediating chemotherapy resistance.Furthermore,EVs-circRNA,a non-invasive biomarker for liquid biopsies,holds significant promise in clinical applications,ranging from early CRC diagnosis to monitoring disease progression and assessing prognosis.These studies provide a new perspective for uncovering CRC pathogenesis and lay the foundation for precision therapy and personalized treatment strategies for CRC.In the future,therapeutic strategies targeting EVs-circRNAs are anticipated to revolutionize CRC treatment,leading to improved therapeutic outcomes and enhanced quality of life for patients.
基金National Natural Science Foundation of China (Grant No. 81800698)Jiangsu Provincial Medical Key Discipline Cultivation Unit (Grant No. JSDW202241)+1 种基金Research Project of Jiangsu Commission of Health (Grant No. H2023053)Zhenjiang Science and the Technology Planning Project (Grant Nos. SH2023006and SH2023008)。
文摘Most papillary thyroid carcinoma(PTC) patients have a good prognosis. However, lymph node metastasis(LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis.Nevertheless, few studies have focused on the underlying mechanisms of LNM. In the current study, we aimed to investigate the potential role of exosomal circRNAs that contribute to LNM in PTC. We identified 9 000 differentially expressed exosomal circRNAs in PTC patients with LNM, including 684 upregulated and 2 193 downregulated circRNAs. Functional enrichment analysis revealed that these differentially expressed circRNAs were primarily involved in a variety of molecular and signaling pathways correlated with PTC progression and LNM. Through bioinformatics analysis, we identified 14 circRNA-miRNA-mRNA networks related to LNM-associated signaling pathways in PTC. Moreover, both circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for their potential involvement in PTC with LNM. Additionally, we identified four upregulated circRNA-related hub genes and eight hub genes correlated with downregulated circRNAs, some of which were validated as being potentially involved in LNM in PTC. Collectively, our findings provide a novel framework for an in-depth investigation of the function of dysregulated exosomal circRNAs and their potential as biomarkers in PTC patients with LNM.
基金supported by grants from the Key Scientific and Technological Projects of Ningbo(No.2021Z133)Ningbo Top Medical and Health Research Program(No.2023020612)+2 种基金National Natural Science Foundation of China(No.81702367)the Medical and Health Research Project of Zhejiang Province(No.2024KY319)the Youth Medical Backbone Talents Training Program of Ningbo.
文摘Circular RNAs(circRNAs)are formed by splicing of precursor RNAs and covalently linked at the 5′and 3′ends.Dysregulated circRNAs are closely related to the epithelial-mesenchymal transition(EMT)of gastrointestinal malignancies.CircRNAs,including circRNA_0008717,circGOT1,circ-DOCK5,circVPS33B,circPVT1,circMET,circ-OXCT1,circ_67835,circRTN4,circ_0087502,circFNDC38,circ_PTEN1,circPGPEP1,and circ-E-Cad are involved in the EMT process of gastrointestinal malignancies through a variety of mechanisms,such as regulating EMT-inducing transcription factors,signaling pathways,and tumor microenvironments.Gastrointestinal(GI)malignancies are common malignant tumors worldwide,and the heterogeneity and easy metastasis of gastrointestinal malignancies limit the effectiveness of medical treatments.Therefore,investigating the molecular mechanisms involved in the pathogenesis of gastrointestinal malignancies is essential for clinical treatment.This article summarizes the biological roles and molecular mechanism of circRNAs in EMT of gastrointestinal malignancies,providing a theoretical basis for applying EMT-related circRNAs in targeted therapy.
基金Supported by The National Natural Science Foundation of China,No.81901819Peking University People’s Hospital Scientific Research Development Funds,No.RDX2024-08Beijing Natural Science Foundation,No.7232187.
文摘BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship between EMVI and expression of the circular RNA hsa_circ_0097977 in orthotopic GC mouse models.METHODS A retrospective analysis was conducted in addition to a preclinical animal study,involving 13 GC patients and 24 orthotopic GC mouse models,respectively.EMVI was assessed using axial T2-weighted fat suppression sequences on a 9.4T magnetic resonance imaging(MRI)with histopathological confirmation as the gold standard for EMVI.The impact of hsa_circ_0097977 on EMVI and GC cell function was evaluated.Statistical analyses comprised consistency,area under the curve analysis,correlation,χ^(2)/Fisher exact,and Mann-Whitney U/t-tests,with significance set at P<0.05.RESULTS EMVI was accurately detected using 9.4T MRI in orthotopic mouse models with an area under the curve of 0.843(sensitivity 78.6%,specificity 90.0%).MRI detected EMVI was the only imaging factor associated with distant metastasis(P=0.04).Furthermore,knockdown of hsa_circ_0097977 was the only factor associated with EMVI(P=0.043,0.038)and led to reduced invasion and increased apoptosis in GC cells.CONCLUSION EMVI,a risk factor for distant metastasis in GC,is detectable by 9.4T MRI and regulated by hsa_circ_0097977,making it a potential therapeutic target.
基金supported by Shanghai Natural Science Foundation(Grant Number 22ZR1456600)Science and Technology Innovation Action Plan in Shanghai on Experimental Animal Research(Grant Number 22140903600)+1 种基金Clinical Research and Cultivation Project of Tongji Hospital in Shanghai(Grant Number ITJ(QN)2201)the National Natural Science Foundation of China(Nos.82227807,81830059)。
文摘Background:Sunitinib resistance is a major challenge in advanced renal cell carcinoma(RCC).Clinically,elucidating the underlying mechanisms and developing practical countermeasures for sunitinib resistance in RCC is desirable.In previous studies,we found that circAGAP1 expression was significantly upregulated in clear cell RCC(ccRCC)and was strongly associated with poor prognosis.However,the role of circAGAP1 in sunitinib resistance in ccRCC remains unclear.Methods:We used public databases for bioinformatics analysis to identify the binding targets of circAGAP1.Additionally,the effects of circAGAP1 on the proliferation,clonogenesis,apoptosis,and migration of ccRCC cells were analyzed using quantitative real-time PCR,cell counting kit-8 assays,migration and apoptosis assays,and colony formation assays.Furthermore,RNA immunoprecipitation,dual-luciferase reporter,and fluorescence in situ hybridization assays were used to explore the molecular mechanism.Results:In this study,circAGAP1 exhibited higher expression in sunitinib-sensitive ccRCC cells and inhibited the clonogenesis,proliferation,and migration of ccRCC cells after sunitinib treatment.Mechanical studies revealed that circAGAP1 regulated the expression of sunitinib target platelet-derived growth factor receptor by acting as a microRNA sponge that suppresses miR-149-5p,miR-455-5p,and miR-15a-5p simultaneously.Overexpression of these three miRNAs reversed circAGAP1-mediated sunitinib sensitivity in ccRCC.Conclusions:In summary,our findings indicate that circAGAP1 may serve as a promising biomarker to predict sunitinib sensibility and a therapeutic target in ccRCC.
文摘Circular RNAs(circRNAs),a new star of noncoding RNAs,are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome.Most circRNAs are conserved throughout species and fre-quently show stage-specific expression during various stages of tissue develop-ment.CircRNAs were a mystery discovery,as they were initially believed to be a product of splicing errors;however,subsequent research has shown that ci-rcRNAs can perform various functions and help in the regulation of splicing and transcription,including playing a role as microRNA(miRNA)sponges.With the application of high throughput next-generation technologies,circRNA hotspots were discovered.There are emerging indications that explain the association of circRNAs with human diseases,like cancers,developmental disorders,and in-flammation,and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases,including cancer.After the discoveries of miRNAs and long noncoding RNAs,circRNAs are now acting as a novel re-search entity of interest in the field of RNA disease biology.In this review,we aim to focus on major updates on the biogeny and metabolism of circRNAs,along with their possible/established roles in major human diseases.
基金supported by the National Natural Science Foundation of China(No.81871835)the Shanghai Frontiers Science Research Base of Exercise and Metabolic Health,and the Shanghai Key Lab of Human Performance(Shanghai University of Sport)(No.11DZ2261100),China.
文摘Bone is a connective tissue that has important functions in the human body.Cells and the extracellular matrix(ECM)are key components of bone and are closely related to bone-related diseases.However,the outcomes of conventional treatments for bone-related diseases are not promising,and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy.Circular RNAs(circRNAs)are single-stranded RNAs that form closed circular structures without a 5’cap or 3’tail and polycyclic adenylate tails.Due to their high stability,circRNAs have the potential to be typical biomarkers.Accumulating evidence suggests that circRNAs are involved in bone-related diseases,including osteoarthritis,osteoporosis,osteosarcoma,multiple myeloma,intervertebral disc degeneration,and rheumatoid arthritis.Herein,we summarize the recent research progress on the characteristics and functions of circRNAs,and highlight the regulatory mechanism of circRNAs in bone-related diseases.
文摘Advancing knowledge of the transcriptome has revealed that circular RNAs(circRNAs)are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles.More interesting is the accumulating evidence which demonstrates the implication of circRNAs in diseases,especially cancers.This revelation has helped to form the rationale for many studies exploring their utility as clinical biomarkers.CircRNAs are highly stable due to their unique structures,exhibit some tissue specificity,and are enriched in exosomes,which facilitate their detection in a range of body fluids.These properties make circRNAs ideal candidates for biomarker development in many diseases.This review will outline the discovery,biogenesis,and proposed functions of circRNAs.
基金supported by the National Natural Science Foundation of China,Nos.81771346,82071383the Taishan Scholar Program of Shandong Province of China,No.tsqn201812156+1 种基金Spring City Leader Talent Support Plan,No.201984Rongxiang Regenerative Medicine Foundation of Shandong University,No.2019SDRX-23(all to BN)。
文摘Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate in the survival and differentiation of multiple nerve cells,and may even promote the recovery of neurological function after stroke.However,their role in the inflammatory response after spinal cord injury remains unclear.In the present study,we established a mouse model of T9 spinal cord injury using the modified Allen’s impact method,and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury.Of these,the expression levels of circPrkcsh were significantly different between injured and sham-treated mice.We then treated astrocytes with tumor necrosis factor-αin vitro to simulate the inflammatory response after spinal cord injury.Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells.We also found that circPrkcsh regulated the expression of the inflammationrelated gene Ccl2.Furthermore,in tumor necrosis factor-α-treated astrocytes,circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression,and reduced the secretion of inflammatory cytokines in vitro.These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs.Furthermore,circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression,which might provide a new potential therapy for SCI.The study was approved by the Animal Ethics Committee of Shandong University of China(approval No.KYLL-20170303)on March 3,2017.
基金supported by the National Natural Science Foundation of China (81500925)
文摘Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ RNAs) have been reported to contribute to the pathogenesis of AD. We found an age-dependent elevation of mi R-138 in APP/PS1(presenilin-1) mice. Mi R-138 inhibited the expression of ADAM10 [a disintegrin and metalloproteinase domain-containing protein 10], promoted amyloid beta(Ab) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice. Overexpression of sirtuin 1(Sirt1), a target of mi R-138, ameliorated the mi R-138-induced inhibition of ADAM10 and elevation of Ab in vitro. The circ RNA HDAC9(circ HDAC9) was predicted to contain a mi R-138 binding site in several databases. Its expression was inversely correlated with mi R-138 in both Ab-oligomertreated N2 a cells and APP/PS1 mice, and it co-localized with mi R-138 in the cytoplasm of N2 a cells. Circ HDAC9 acted as a mi R-138 sponge, decreasing mi R-138 expression, and reversing the Sirt1 suppression and excessive Ab production induced by mi R-138 in vitro. Moreover,circ HDAC9 was decreased in the serum of both AD patients and individuals with mild cognitive impairment.These results suggest that the circ HDAC9/mi R-138/Sirt1 pathway mediates synaptic function and APP processing in AD, providing a potential therapeutic target for its treatment.
文摘As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.
基金Supported by the Natural Science Foundation of Jiangsu Province,No.BK20161232the Suzhou Special Project of Diagnosis and Treatment for Key Clinical Disease,No.LCZX201715
文摘BACKGROUND Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level,circular RNAs(circRNAs)participate in the pathogenesis of a variety of diseases and are considered ideal biomarkers of human disease.AIM To examine the expression of circRNA_103516 in inflammatory bowel disease(IBD)and its associations with clinical phenotypes and inflammatory cytokines.METHODS Peripheral blood mononuclear cells(PBMCs)were obtained from patients with IBD,healthy controls(HCs),and patient controls(PCs).Expression of circRNA_103516 and hsa-miR-19b-1-5p was assessed by quantitative reverse transcription-polymerase chain reaction.Crohn's disease activity index(CDAI),Mayo score,C-reactive protein(CRP)level,and erythrocyte sedimentation rate(ESR)were measured.To assess the inflammatory cytokines tumour necrosis factorα(TNF-α),interferon-γ(IFN-γ),and interleukin-10(IL-10),blood samples were analysed by flow cytometry.RESULTS Ninety Crohn’s disease(CD)and 90 ulcerative colitis(UC)patients,80 HCs,and 35 PCs were included in the study.CircRNA_103516 was upregulated in CD and UC patients compared with HCs and PCs(P<0.05).The area under the curve of circRNA_103516 for diagnosing CD and UC was 0.790 and 0.687,respectively.In addition,circRNA_103516 levels were increased in active CD and UC compared with remittent groups(P=0.027,P=0.045).Furthermore,in CD,circRNA_103516 correlated positively with CDAI(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),and IFN-γ(P<0.001)and negatively correlated with IL-10(P=0.006).In UC patients,circRNA_103516 correlated with Mayo score(P<0.001),CRP(P<0.001),ESR(P<0.001),TNFα(P<0.001),IFN-γ(P=0.011),and IL-10(P=0.002).Additionally,circRNA_103516 correlated positively with stricturing(P=0.018)and penetrating(P=0.031)behaviour.Moreover,hsamiR-19b-1-5p correlated negatively with circRNA_103516 in CD.CONCLUSION CircRNA_103516 levels in PBMCs can be considered an ideal candidate biomarker for diagnosing IBD.Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.
