环状RNA在肿瘤中的表达与功能

环状RNA(circular RNA,circRNA)是一类闭合环状的内源RNA分子,广泛存在于不同物种及多种人体细胞中,具有丰富性、稳定性和组织特异性等特点。人体细胞中的circRNA主要可分为外显子circRNA、环状内含子RNA和外显子-内含子circRNA等。与正常组织相比,circRNA在多种肿瘤组织中异常表达,并具有作为微小RNA(microRNA,miRNA)海绵调控miRNA、结合蛋白质、参与翻译等功能。虽然circRNA在肿瘤中异常表达的具体机制尚不明确,但其在食管鳞状细胞癌、胃癌、结直肠癌、肝细胞癌、神经胶质瘤等多种肿瘤发生、发展的分子通路中具有重要作用,并有望成为全新的肿瘤标志物和治疗靶点。circRNA领域的发展日新月异,本文根据最新研究报道,就circRNA的基本特征、异常表达机制、调控肿瘤的机制及其在多种肿瘤中发挥的作用作一综述。     

环状RNA的生物学功能及其在胃肠肿瘤发生中的作用

环状RNA(circular RNA,circ RNA)是广泛存在于真核生物转录组的内源性非编码RNA.与线性RNA不同,circ RNA不易被酶解,具有更加稳定的结构.circ RNA具有微小RNA(micro RNA,mi RNA)海绵、RNA结合蛋白海绵、调节转录以及翻译蛋白质等多种生物学功能,能够在转录水平或转录后水平调节基因的表达.近期的研究发现,circ RNA在调控肿瘤细胞增殖、迁移和侵袭过程中扮演着重要的角色.胃肠肿瘤是我国常见且死亡率高的恶性肿瘤,研究者在胃肠肿瘤中发现大量异常表达的circ RNA(如:hsa_circ_0014717、hsa_circ_0001017、hsa_circ_0061276、hsa_circ_0125965和hsa_circ_KLDHC10等).本文首先阐述circ RNA的形成机制和生物学功能;然后结合国内外胃肠肿瘤相关circ RNA的最新研究进展和本课题组相关研究成果,对circ RNA影响胃肠肿瘤发生的机制作一综述,并希望能以此为胃肠肿瘤的诊断和治疗提供新的理论依据.     

环状RNA翻译在癌症中的研究进展

环状RNA是一类有着独特环状结构的非编码RNA,它在生物体内有微小RNA分子海绵、蛋白质脚手架、调控基因转录、调控可变剪接、进入外泌体等多种经典功能机制。虽然环状RNA被定义成一种非编码RNA,但随着生物信息学和翻译组学的发展与应用,越来越多的研究发现,环状RNA是能够被翻译的。该文介绍了现在主要的环状RNA翻译的调控机制,总结了目前研究环状RNA翻译的常用数据库,汇总了环状RNA翻译的蛋白质和多肽在癌症中的最新发现,讨论了环状RNA翻译的应用前景和问题,旨在促进发现更多由环状RNA编码的与肿瘤相关的蛋白质和多肽。     

外泌体环状RNA在泌尿系统肿瘤中的研究进展

外泌体是一种包含了复杂RNA和蛋白质的膜性囊泡，其主要来源于细胞内溶酶体微粒内陷形成的多囊泡体，经多囊泡体外膜与细胞膜融合后释放到胞外基质中。外泌体在肿瘤微环境中介导细胞间通讯，其功能取决于来源的细胞类型。环状RNA是一类由前体mRNA反向剪接生成的非编码RNA，在外泌体中富集且稳定表达。外泌体环状RNA在疾病中发挥了重要的调控作用，其作为肿瘤标志物和治疗靶点的临床应用前景与价值现已成为研究热点。本文就外泌体环状RNA在泌尿系统肿瘤中的研究进展作一综述。     

环状RNA在胃癌与结直肠癌中的功能和作为临床标志物的潜力

环状RNA（circRNA）是一种广泛存在于生物体内的新型内源性RNA。CircRNA由RNA前体可变剪接产生,比线性RNA有更好的稳定性,是最近几年RNA领域的明星分子。CircRNA来源于内含子或外显子,可充当miRNA海绵或者结合蛋白质来参与基因表达调控,甚至已发现有circRNA能编码蛋白质。越来越多的研究表明,circRNA在肿瘤（如：食管癌、肝癌、胃癌、结直肠癌和膀胱癌等）的发生发展中发挥了重要作用。近年来,circRNA在胃癌、结直肠癌的研究逐渐增加,circRNA可能成为新的生物学标志物发挥诊断和预后的作用。本文将主要介绍circRNA 在胃癌及结直肠癌的功能和作为临床标志物的研究进展。     

环状RNA的结构和功能特性及其与胃癌发生的关系

环状RNA是一类新发现以共价键形成环状结构的RNA分子,没有5'帽和3'尾,具有高度的序列保守性和稳定性,不易被核酸外切酶降解,在转录或转录后水平发挥基因表达调控的作用。近年来,已发现环状RNA与许多肿瘤包括胃癌发生密切相关。首先介绍环状RNA形成、分类、分子特征和功能,然后从环状RNA与胃癌发生、环状RNA与胃癌诊断、以及环状RNA在胃癌治疗中的作用等三个方面阐述环状RNA与胃癌的关系。     

CircRNA肿瘤相关生物学功能的研究进展

环状RNA(circRNA)是一类具有环状结构的非编码RNA(noncoding RNAs, ncRNA),广泛存在于多种生物细胞中,具有结构稳定、序列保守及细胞或组织特异性表达等特征。已被证实circRNA在许多癌症中存在表达异常,参与了恶性肿瘤的发生发展。CircRNA在细胞中的分布与其功能发挥密切相关。研究表明,胞核分布的circRNA可以参与调节mRNA转录和表观遗传调控,胞质分布的circRNA具有充当"miRNA海绵"、与RNA结合蛋白结合、影响蛋白质翻译、编码蛋白质等功能。本文对circ RNA在肿瘤中发挥的相关生物学功能进行综述,以期为后续研究提供一定的理论依据。     

环状RNA在肝细胞癌中的作用及机制

肝细胞癌（hepatocellular carcinoma,HCC）治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA（exonic circRNA,ecircRNA）、环状内含子RNA（circular intronic RNA,ciRNA）及外显子 内含子circRNA（exon-intron circRNA,EIciRNA）三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。     

环状RNA在肝细胞癌中的作用及机制

肝细胞癌（hepatocellular carcinoma,HCC）治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA（exonic circRNA,ecircRNA）、环状内含子RNA（circular intronic RNA,ciRNA）及外显子 内含子circRNA（exon-intron circRNA,EIciRNA）三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。     

真菌环状RNA鉴定及研究展望

环状RNA是一类具有丰富调节潜力的闭合环状单链RNA,其可以通过竞争性结合内源RNA、充当蛋白质支架以及翻译模板等方式,从而参与基因表达调控。本文综述了真菌环状RNA的鉴定流程和难点,为后续解析环状RNA在真菌发育与代谢等过程中的调节作用提供理论支持。     

circRNA and gastrointestinal cancer

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that form covalently closed continuous loops without 3′ end poly (A) tails and 5′ end caps. circRNAs are more conservative and stable than linear RNA. circRNAs can specifically bind to microRNAs as competing endogenous RNA, thereby directly or indirectly regulating the expression of related genes. circRNAs have been implicated in several cancers including gastrointestinal (GI) cancers. Some circRNAs have the potential to become biological biomarkers and therapeutic targets of GI cancers. However, the multiple functional roles of circRNAs in GI cancers remain largely unclear.     

CircRNAs: role in human diseases and potential use as biomarkers

Circular RNAs (circRNAs) are a class of endogenous RNAs characterized by a covalent loop structure. In comparison to other types of RNAs, the abundance of circRNAs is relatively low but due to the circular configuration, their stability is very high. In addition, circRNAs display high degree of tissue specificity. The sponging activity of circRNAs toward microRNAs is the best-described mode of action of circRNAs. However, the ability of circRNAs to bind with specific proteins, as well as to encode short proteins, propose alternative functions. This review introduces the biogenesis of circRNAs and summarizes the roles played by circRNAs in human diseases. These include examples of their functional roles in several organ-specific cancers, such as head and neck and breast and lung cancers. In addition, we review potential functions of circRNAs in diabetes, cardiovascular, and neurodegenerative diseases. Recently, a growing number of studies have demonstrated involvement of circRNAs in a wide spectrum of signaling molecular pathways, but at the same time many different and controversial views on circRNAs role and function are emerging. We conclude by offering cellular homeostasis generated by networks comprising circular RNAs, other non-coding RNAs and RNA-binding proteins. Accordingly, it is predictable that circRNAs, due to their highly stable nature and remarkable tissue specificity, will emerge as reliable biomarkers of disease course and treatment efficacy.Subject terms: Cancer, Cell biology, Molecular biology     

环状RNA翻译蛋白在癌症中的研究进展北大核心CSCD

环状RNA(circular RNA,circRNA)是一种单链环状闭合RNA分子,由线性RNA通过反向剪接形成,具有稳定、高度保守、组织特异性等特点。circRNA能够通过形成竞争性内源性RNA、结合蛋白等多种方式参与机体的生理、病理过程。最近发现,circRNA分子可以通过翻译形成多肽或蛋白参与癌症的发生和发展。circRNA是人类癌症中有前途的诊断和预后标志物,也是癌症治疗的潜在药物靶点。本文重点介绍了circRNAs编码的多肽和蛋白质在多种癌症中的相关研究进展。这些多肽和蛋白质分别依赖内部核糖体进入位点和m6A两种不同的机制进行翻译。我们还总结了circRNA编码的多肽和蛋白质在各种癌症的诊断、治疗、预后和机制研究中的潜在用途。     

Exosomal circRNAs as novel cancer biomarkers: Challenges and opportunities

Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.     

CircRNA: a rising star in plant biology

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, binding miRNAs or proteins, and being translated into proteins, which are important for cell proliferation and cell differentiation, individual growth and development, as well as many other biological processes. However, compared with that in animal models, studies of circRNAs in plants lags behind and, particularly, the regulatory mechanisms of biogenesis and molecular functions of plant circRNAs remain elusive. Recent studies have shown that circRNAs are wide spread in plants with tissue- or development-specific expression patterns and are responsive to a variety of environmental stresses. In this review, we summarize these advances, focusing on the regulatory mechanisms of biogenesis, molecular and biological functions of circRNAs, and the methods for investigating circRNAs. We also discuss the challenges and the prospects of plant circRNA studies.     

Profiling of circular RNAs and circTPCN/miR-634/mTOR regulatory pathway in cervical cancer

Circular RNAs (circRNAs) are highly stable forms of endogenous non-coding RNA molecules with diverse biological functions. Some of them have been demonstrated to play crucial roles in the initiation or development of cancers through regulation of gene expression. However, the profiles and the roles of circRNAs in tumorigenesis of cervical cancer remain largely unknown. In the current study, we investigated the expression profiles of circRNAs and their potential oncogenic mechanisms in cervical cancer. The expression patterns, obtained using a microarray assay, revealed a total of 192 differentially expressed circRNAs, of which 106 were upregulated and 86 were downregulated, in cervical cancer samples compared with normal cervical samples. The differential expression of circRNAs was validated using quantitative real-time polymerase chain reaction. Two circRNAs (circTPCN and circFAM185A) were confirmed to be significantly upregulated in cervical cancer samples, indicating that they represent potential biomarkers of cervical cancer. The role and the potential molecular mechanism of circTPCN in cervical cancer tumorigenesis were further investigated. Knockdown of circTPCN significantly suppressed proliferation, migration, and invasion and increased apoptosis of cervical cancer cells in vitro. Molecular analysis revealed that circTPCN acted as a sponge of miR-634 to enhance mTOR expression. Thus, the circTPCN/miR-634/mTOR regulatory pathway might be involved in cervical cancer tumorigenesis, and circTPCN is a potential therapeutic target in cervical cancer.     

circRNAs在植物中的研究进展

circular RNA(circRNA)是一类具有闭合环状结构的内源性非编码RNA,广泛存在于多种真核生物中,具有结构稳定、序列保守、表达特异性等特征。研究表明circRNAs可作为海绵(sponge)吸附microRNA(miRNA)并参与其表达调控过程,也可通过与蛋白互作调控基因表达等生物过程;发现circRNAs不仅参与植物激素信号转导等生理过程,而且还能在植物响应逆境胁迫中起到重要作用。该文主要对近年来国内外有关circRNAs的类型、形成机制、功能及其在植物生长发育过程中的研究进展进行了综述,并讨论了circRNAs的研究意义及存在的问题,为进一步研究circRNAs在植物中的作用机制及其基因调控网络提供参考。     

BORIS-mediated generation of circular RNAs induces inflammation

Circular RNAs (circRNAs), which are more stable than linear mRNAs and long non-coding RNAs (LncRNAs), are detected in body fluids such as plasma, serum, and exosomes. Disease-associated circRNAs have significant clinical roles due to their diagnostic and prognostic values. Brother of regulator of imprinting site (BORIS) promotes cancer progression and is specifically highly expressed in the majority of carcinoma. However, the mechanism underlying the regulation of circRNAs by the oncoprotein BORIS and their role in regulating inflammation and immunity remain to be further explored. Vaccines prepared from circRNAs extracted from cancer cells showed that circRNAs induced inflammation and prevented cancer progression. Serum from animals injected with cancer cell-derived circRNAs vigorously reacted with cells that expressed cancer-specific antigen BORIS or cancer extracted circRNAs. It has been implicated that cancer-related circRNAs could be used as antigens to activate immune responses to prevent cancers and stimulate NF-κB signaling pathway by up-regulating and inducing TLR3. In the study we also found that BORIS regulated the expression of circRNAs and interacted with RNA motifs and the CCCTC binding factor (CTCF) motif adjacent to circRNA splicing sites to enhance the formation of circRNAs. Thus, our study delineated the novel mechanism by which cancer-specific antigen BORIS regulated circRNAs and identified that circRNAs could serve as a vaccine for cancer prevention.     

环状RNA及其在生态毒理学研究中的应用进展

环状RNA（circular RNAs,circRNAs）是一类共价闭合环状非编码RNA,具有进化上保守、结构上稳定、组织特异性表达等特点。CircRNAs可作为miRNAs海绵影响其对基因的调控,还可与RNA结合蛋白（RNA binding proteins,RBPs）相互作用,也有研究表明某些circRNAs还具有被翻译成蛋白质的潜能。CircRNAs已被证实对某些疾病具有特异性、稳定性和调节功能,如癌症、糖尿病、心血管疾病、神经退行性疾病等,其可作为潜在的诊断、预后生物标志物和治疗靶点。最近,有研究发现circRNAs参与了环境化学污染物诱导的毒性效应发生及发展的过程。目前,生态毒理学研究中评价环境化学污染物和毒效应之间关系的毒性终点通常会受遗传多态性和表观遗传学影响,考虑到经环境化学污染物暴露后生物体内circRNAs差异性表达的现象,或许在生态毒理学研究中circRNAs也有作为生物标志物的可能性。基于此,对circRNAs的生物合成与降解、生物学功能、分析方法及其目前在生态毒理学研究中的应用展开综述,并对其作为分子生物标志物在环境污染物暴露早期诊断和生态风险评价中的应用进行了展望,以期为生态毒理学研究和环境风险评价提供参考。