Circular RNA circ_0003609 ameliorates hypertrophied ligamentum flavum by regulating the miR-155/SIRT1 axis

Background:Hypertrophy of the ligamentumflavum(HLF)is a common contributor to spinal stenosis which results in significant neurological impairments.Circular RNA(circRNA)circ_0003609 has been linked to HLF;however,the exact mechanism by which it causes this disease is unclear.Methods:Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference.Cell proliferation andfibrosis-related gene expression were checked by the Cell Counting Kit-8(CCK-8)assay and western blotting.CircBank’s prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment.The function of the miR-155/sirtuin 1(SIRT1)axis in controlling HLFfibrosis was further examined.Results:Overexpression of circ_0003609 suppressed HLF cell propagation andfibrosis compared to its silencing.It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled thefibrosis of HLF cells.It was found that circ_0003609 acted as a sponge for miR-155,regulating thefibrosis of HLF cells.Further,miR-155 targets SIRT1,and the miR-155/SIRT1 axis promotes HLF cellfibrosis.Conclusion:Circ_0003609 ameliorates hypertrophied ligamentumflavum(LF)by modulating the miR-155/SIRT1 axis,indicating a potential treatment approach for HLF.

Advances of N6-methyladenosine modification on circular RNA in hepatocellular carcinoma

N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modification of m6A regulates RNA transcription, processing, splicing, degradation, and translation, and plays an important role in the biological process of tumors. Circular RNA, which lacks the 5' cap structure, has been mistakenly regarded as a "junk sequence" generated by accidental shearing during the transcription process. However, it has been found that circRNAs can be involved in tumor invasion and metastasis through microRNAs, binding proteins, translated peptides, and m6A modifications. In this paper, we reviewed the role of m6A modifications in circRNA regulation and their functions in hepatocellular carcinoma and discussed their potential clinical applications and future development in this field.

Circular RNA: The evolving potential in the disease world

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.

Analysis of the Effects of Different Synthesis and Processing Methods on Circular RNA Integrity,Protein Expression,and Removal of Immunogenic Impurities

Circular RNAs(circRNAs)are emerging as a promising alternative to messenger RNAs(mRNAs)in gene delivery applications due to their enhanced stability and translation.Developing circRNA-based therapeutic platforms requires efficient manufacturing of circRNA with broad scalability.However,the permuted intron-exon(PIE)-based circRNA production commonly used to date involves complex RNA synthesis,circularization,precursor RNA digestion,and impurity removal steps that have limited practical applications.While co-transcriptional circularization could effectively streamline circRNA production,and both cellulose/phosphatase treatment and high-performance liquid chromatography(HPLC)have demonstrated their reliability in mRNA manufacturing,their potential effects on the quality,translation,and reactogenicity of circRNA remained to be fully investigated.Here,using circRNAs systematically manufactured through three independent workflows,we comprehensively examined the utilities of these RNA synthesis and processing methods in circRNA production by comparing the integrity,translation,and immunogenicity of their circRNA products.We began by manufacturing a mNeonGreen(mNG)-encoding circRNA through these workflows and subsequently assessed circRNA integrity via E-gel EX electrophoresis.Protein expression was then monitored in HEK 293T,A549,and DC2.4 cells at 72 hours post-transfection.Finally,we evaluated the immunogenicity of these circRNAs by measuring their interferon beta(IFN-β)induction in A549 cells at 4 hours post-transfection.Using HPLC purification over cellulose and phosphatase treatment resulted in 10-14%higher circRNA enrichment by reducing nicking associated with processing conditions.Protein expression remained consistent across circRNAs from different workflows(P>0.05),demonstrating that co-transcriptional circularization produces circRNA with translation levels comparable to those obtained from the conventional PIE method.Moreover,both cellulose/phosphatase treatment and HPLC purification effectively minimized IFN-βinduction of the purified circRNAs,confirming their reliability in removing immunogenic impurities introduced during in vitro transcription and their compatibility with the co-transcriptional circularization strategy.Collectively,our results provide valuable insights for improving the production efficiency and scalability of circRNA manufacturing that are crucial for addressing key bottlenecks in the development of circRNA-based therapeutic applications.

Biological functions and potential implications of circular RNAs

Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.

Circular RNAs:Diagnostic and Therapeutic Perspectives in CNS Diseases

Circular RNAs(circRNAs)are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends.A growing body of evidence suggests that circRNAs play important roles in physiology and pathology.In particular,accumulating data on circRNA functions in various central nervous system(CNS)diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders.In this review,we focus on the regulatory and functional roles of circRNAs in CNS diseases,highlighting their diagnostic and therapeutic potential,with the aim of providing new insights into CNS diseases.

Circular RNA expression and the competitive endogenous RNA network in pathological,age-related macular degeneration events:A cross-platform normalization study

Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database.We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis.Peroxisome and tumor necrosis factor-α(TNF-α)signaling and nuclear factor kappa B(NF-κB)were among the top 10 pathways,and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs(circRNAs).We then constructed a competing endogenous RNA network,which is related to differentially expressed circRNAs.This network included seven circRNAs,15 microRNAs,and 82 mRNAs.The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1(HIF-1)signaling pathway was a common downstream event.The results of the current study may provide insights into the pathological processes of atrophic AMD.

Circular RNAs在肿瘤细胞程序性死亡中的研究进展

Circular RNAs(circRNAs)是由真核生物中数千个基因的前体mRNA反向剪接形成的一类共价闭合的连续环状结构的单链闭合RNA分子。高通量测序和生物信息学方法揭示了circRNAs在物种间的广泛表达。它们的高度稳定性、丰度和物种间的进化保守性表明它们具有独特的特性和多样的细胞功能,如高效与microRNA(miRNA)形成海绵机制。同时,circRNAs在调节转录和剪接方面也起着重要作用。细胞程序性死亡是维持人体正常发育和内环境稳态所必需的过程,它的主要功能是消除受损、感染或老化的细胞,一般有多种形式,包括细胞凋亡、细胞焦亡、铁死亡以及自噬等。研究显示,大多数circRNAs在病理条件下以组织特异性方式异常表达,如调节肿瘤细胞的程序性细胞死亡事件,参与肿瘤进展。本文概述circRNAs在肿瘤细胞程序性死亡中的研究进展以及circRNA作为新治疗靶点的未来应用。

Circular RNA LPAR3通过miR-143-5p/USP14通路调控食管癌细胞糖酵解的研究

目的探究调控食管癌细胞糖酵解的机制。方法逆转录实时定量PCR(quantitative real-time,qRT-PCR)法分别检测环状RNA溶血磷脂酸受体(circular RNA lysophosphatidic acid receptor 3,CircLPAR3),微小RNA-143-5(microRNA-143-5p,miR-143-5p)和泛素特异性蛋白酶14(ubiquitin-specific protease 14,USP14)的表达水平;使用Seahorse XF 24细胞外通量分析仪测量细胞外酸化率(extracellular acidification rate,ECAR)和耗氧率(oxygen comsumpition rate,OCR);Western印迹法检测糖酵解途径关键酶HK2的表达水平;使用Starbase数据库预测CircLPAR3与miR-143-5p以及miR-143-5p与USP14的靶向结合位点,双荧光素酶试验验证CircLPAR3和miR-143-5p以及miR-143-5p与USP14的靶向关系。结果与正常人食管上皮细胞(normal human esophageal epithelial cells,Het-1A)组比较,食管癌细胞系中CircLPAR3高表达,且KYSE450细胞系的表达最高,同时miR-143-5p低表达而USP14高表达。与Het-1A组比较,KYSE450组HK2的蛋白表达水平增加,同时细胞ECAR增加,整体糖酵解OCR减少;敲低CircLPAR3的表达导致细胞HK2的蛋白表达水平减少,ECAR减少,整体糖酵解OCR增加;在抑制CircLPAR3的表达情况下,抑制miR-143-5p的表达能够部分逆转细胞的糖酵解途径;双荧光素酶实验验证了CircLPAR3和miR-143-5p的靶向关系,以及miR-143-5p和USP14的靶向关系。结论CircLPAR3能够通过调控miR-143-5p/USP14通路调节食管癌细胞糖酵解途径。

Circular RNA hsacirc0000745 may serve as a diagnostic marker for gastric cancer

AIM To determine whether circular RNAs(circ RNAs) are involved in pathological processes of gastric cancer(GC).METHODS Three circ RNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction(q RT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circ RNAmi RNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by q RT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC.RESULTS Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues(P < 0.001) and in plasma samples from patients with GC vs healthy controls(P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-nodemetastasis stage. The area under the ROC curve(AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen(CEA) level increased the AUC to 0.775.CONCLUSION Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer

AIM To analyze the diagnostic value of a circular RNA(circR NA), circ-LDLRAD3, in pancreatic cancer.METHODS Expression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcriptionpolymerase chain reaction(q RT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic(ROC) curve analysis.RESULTS Circ-LDLRAD3 was up-regulated in pancreatic cancer cell lines(P < 0.01), pancreatic cancer tissues(P < 0.01), and plasma samples from patients with pancreatic cancer(P < 0.01). High expression of circLDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738(alone) and 0.7049(alone), and 0.8033(combination) and 0.9355(combination), respectively.CONCLUSION These data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.

Circular RNAs in colorectal cancer:Possible roles in regulation of cancer cells

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.

Novel circular RNA expression profile of uveal melanoma revealed by microarray

Objective: The present study aimed to investigate circular RNA(circRNA) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circRNA in five UM samples and five normal uvea tissues.Next,bioinformatics analyses,including gene ontology(GO) analysis and pathway analysis,were applied to study these differentially expressed circRNAs to predict pathogenic pathways that may be involved.Quantitative real-time polymerase chain reaction(qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circRNA expression profiles obtained from the microarray data.Finally,we analyzed the interaction between validated circRNAs and their potential cancer-associated miRNA targets.Results: In total,50,579 circRNAs [fold change(FC) ≥2.0; P<0.05],including 20,654 up-regulated and 29,925 down-regulated circRNAs,were identified as differentially expressed between UM tissues and normal uvea tissues.We used qRT-PCR to verify seven dysregulated circRNAs indicated by the microarray data,including hsacirc0119873,hsacirc0128533,hsacirc0047924,hsacirc0103232,hsa-circRNA10628-6,hsacirc0032148 and hsacirc0133460,which may be promising candidates to study future molecular mechanisms.Conclusions: This study explored,for the first time,the abnormal expression of circRNAs in UM and described the expression profile of circRNAs,providing a new potential target for the mechanism of UM and future treatment of UM.

Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p

BACKGROUND Recent studies have demonstrated that circular RNA AKT3(circAKT3)plays a crucial role in regulating the malignant phenotypes of tumor cells.However,the potential effects of circAKT3 on esophageal cancer have not been investigated.AIM To illuminate the role of circAKT3 in malignant behaviors of esophageal cancer cells and its underlying mechanism.METHODS Clinical samples were collected to detect the expression of circAKT3.The role of circAKT3 in proliferation,migration,invasion,and apoptosis of esophageal cancer cells was evaluated using Cell Counting Kit-8,wound healing assays,Transwell assays,and fluorescence analysis,respectively.The target of circAKT3 was screened and identified using an online database and luciferase reporter assay.A xenograft nude mouse model was established to investigate the role of circAKT3 in vivo.RESULTS In vitro assays showed that proliferative,migratory,and invasive capacities of esophageal cancer cells were significantly enhanced by circAKT3 overexpression.Furthermore,miR-17-5p was screened as the target of circAKT3,and miR-17-5p antagonized the effects of circAKT3 on esophageal cancer cells.Moreover,we identified RHOC and STAT3 as the direct target molecules of miR-17-5p,and circAKT3 facilitated expression of RHOC and STAT3 by inhibiting miR-17-5p.In vivo assays showed circAKT3 knockdown inhibited growth of esophageal cancer.CONCLUSION CircAKT3 contributed to the malignant behaviors of esophageal cancer in vitro and in vivo by sponging miR-17-5p thus providing a potential target for treatment of esophageal cancer.

Genome-wide map of N6-methyladenosine circular RNAs identified in mice model of severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options.N6-methyladenosine(m6A)modification of circRNAs plays important roles in physiological and pathological processes.However,the roles of m6A circRNA in the pathological process of SAP remains unknown.AIM To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP.METHODS The SAP in C57BL/6 mice was induced using 4%sodium taurocholate salt.The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing.The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNAmicroRNA networks.The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP.RESULTS Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing,of which 32 were upregulated and 25 downregulated.Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP,such as regulation of autophagy and protein digestion.In m6A circRNA–miRNA networks,several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs,such as miR-24-3p,miR-26a,miR-92b,miR-216b,miR-324-5p and miR-762.Notably,the total m6A level of circRNAs was reduced,while the demethylase alkylation repair homolog 5 was upregulated in SAP.CONCLUSION m6A modification of circRNAs may be involved in the pathogenesis of SAP.Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

Biological roles and potential clinical values of circular RNAs in gastrointestinal malignancies

Circular RNAs(circ RNAs),a class of endogenous RNA molecules,are produced by alternative splicing of precursor RNA and are covalently linked at the 5′and 3′ends.Recent studies have revealed that dysregulated circ RNAs are closely related to the occurrence and progression of gastrointestinal malignancies.Accumulating evidence indicates that circ RNAs,including circ PVT1,circ LARP4,circ-SFMBT2,cir-ITCH,circ RNA_100782,circ_100395,circ-DONSON,hsa_circ_0001368,circ NRIP1,circ FAT1(e2),circ CCDC66,circ SMARCA5,circ-ZNF652,and circ_0030235 play important roles in the proliferation,differentiation,invasion,and metastasis of cancer cells through a variety of mechanisms,such as acting as micro RNA sponges,interacting with RNA-binding proteins,regulating gene transcription and alternative splicing,and being translated into proteins.With the characteristics of high abundance,high stability,extensive functions,and certain tissue-,time-and diseasespecific expressions,circ RNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.

Circular RNAs in pulmonary hypertension:Emerging biological concepts and potential mechanism

Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.

胶质瘤中Circular RNA PRKCI的表达及预后相关影响因素研究

目的:探讨Circular RNA PRKCI在脑胶质瘤中的表达及其预后意义。方法:通过定量逆转录聚合酶链式反应检测Circular RNA PRKCI在61例脑胶质瘤组织及正常脑组织中的表达水平,并绘制Kaplan-Meier曲线、对数秩检验和Cox分析,以阐明Circular RNA PRKCI的临床意义。结果:与正常组织相比,Circular RNA PRKCI在胶质瘤患者中的表达增高(P<0.001),且Circular RNA PRKCI表达上调与WHO分级的增高有关(P=0.017)。Kaplan-Meier分析结果显示,Circular RNA PRKCI高表达患者的5年存活率明显低于低表达Circular RNA PRKCI的患者(P=0.0309)。Cox单因素和多因素分析显示,Circular RNA PRKCI过度表达(P<0.001)可作为胶质瘤患者预后的独立影响因素。结论:Circular RNA PRKCI在胶质瘤组织中高表达,且高Circular RNA PRKCI表达的患者预后不良,提示Circular RNA PRKCI可能是胶质瘤患者相关预后判断和治疗的潜在靶点。

Emerging roles of circular RNAs in retinal diseases

Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the retina.Current research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal degeneration.In this review,we explore a relatively new field of research involving circular RNAs,whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just emerged.While knowledge of circular RNAs function is limited given its novelty,current evidence has highlighted their roles as modulators of microRNAs,regulators of gene transcription,and biomarkers of disease development and progression.Here,we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy,glaucoma,proliferative vitreoretinopathy,and age-related macular degeneration.Further,we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.

Regulatory RNAs,microRNA,long-non coding RNA and circular RNA roles in colorectal cancer stem cells

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.