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在胃癌中的研究现状与策略

环状RNA (circRNA)是一种共价闭合的非编码RNA,可以调节真核生物中的基因表达.最近应用高通量RNA测序和生物信息学方法揭示人类细胞中存在大量circRNA.许多circRNA具有一定的组织和时序特异性,且与生理发育和各种肿瘤等疾病密切相关. circRNA被证明在细胞质中富集和稳定,表明其具有作为肿瘤生物标志物的潜力.胃癌(gastric carcinoma,GC)是一种常见的恶性肿瘤,在全球癌症相关死亡原因中排第3位.尽管该疾病在诊断和治疗方面取得了许多进展,但GC患者的预后仍然很差,大多数国家的5年总生存率低于30%.因此,寻找能调节GC发生发展和评估预后的新分子机制和治疗靶标至关重要.近年来circRNA在胃癌中的研究不断增多,其在胃癌的发生发展、诊断、治疗及预后过程中扮演重要角色.本文就circRNA产生机制及一般特征、生物学功能、在胃癌中的研究进展及研究中存在的问题作一综述.     

环状RNA作为生物标志物的研究进展

环状RNA(circRNA)是一种共价闭合环状结构的非编码RNA,与线性RNA有显著差别。circRNA通过外显子或内含子的反向剪接进而环化形成完整的环形结构。近年研究已证实circRNA在基因的表达调控和肿瘤等疾病的发生和发展中发挥着重要作用,提示circRNA可能具有巨大的临床诊疗价值。就circRNA的形成、特征、功能,特别是其作为肿瘤生物标志物的研究进展做简要综述。     

EBV编码miRNAs在病毒感染和肿瘤发生中的功能和意义

EB病毒(Epstein-Barr virus,EBV)是一种172 kb大小的线性双链DNA病毒,与鼻咽癌、淋巴瘤、胃癌等恶性肿瘤的发生密切相关. EBV编码的微小RNAs (miRNAs)可以调节病毒和宿主细胞基因的表达,并且在癌症发生发展中起着多种作用.本文综述了EBV编码的miRNAs (EBV-encoded miRNA,EBV miRNAs)在病毒感染和肿瘤发生、侵袭转移、抗凋亡、信号通路等方面的生物学功能,以及对于EBV相关肿瘤诊断标志物的潜在意义. EB病毒编码的miRNAs也可能成为进一步研究EBV相关肿瘤治疗的一个候选靶点.     

环状RNA的研究进展

环状RNA(Circular RNA,circRNA)是一类具有闭合环状结构的内源性非编码RNA(noncodingRNA,ncRNA),主要由前体RNA(pre-mRNA)通过可变剪切加工产生,circRNA广泛存在于所有真核生物中,并且非常稳定。目前,circRNA的研究已经成为了RNA研究领域的新热点,研究发现circRNA在转录本中占有相当大的比例,有的表达丰度甚至显著高于其他转录本。同时,circRNA对基因的表达有重要调控作用,在生物的发育进程中发挥了重要的生物学功能,如充当miRNA海绵、作为内源性RNA以及生物标记物,在疾病的诊断与治疗中也发挥重要作用。研究发现circRNA在一些疾病的发生中扮演了重要角色,包括动脉硬化、神经系统紊乱、糖尿病和癌症的发生。综述了circRNA的研究进展,阐述了circRNA的研究历史、circRNA的特点、形成过程、表达情况、circRNA与疾病间的关系以及circRNA的功能,并讨论了circRNA的研究意义及存在的问题。     

环状RNA在纤维化疾病中的调控机制及其应用的研究进展

纤维化是指细胞外基质成分的过量沉积,最终导致器官结构的破坏和功能丧失。环状RNA (circular RNA, circRNA)是一类内源性非编码RNA,其特征在于以共价键形成封闭环状结构。circRNA在真核生物体内分布广泛,具有一定的生物稳定性、保守性以及组织特异性。近年来研究表明,circRNA在纤维化疾病的发生发展中发挥着极其重要的作用,因此circRNA的表达异常可能为纤维化疾病的早期诊断和预后评估提供依据以及为纤维化疾病的治疗提供潜在的靶点。该文总结了circRNA的分类、功能、在纤维化疾病中的调控作用及其应用情况。     

病毒致癌相关microRNA的研究进展

microRNA(miRNA)是一类内源性非编码的小RNA,广泛存在于病毒、植物和动物等生物体内。miRNA通过与目标mRNA互补配对,对基因进行转录后的表达调控,在生物体的发育、增殖、分化和凋亡等方面发挥重要的生理作用。最近的研究表明,miRNA与病毒介导的肿瘤之间存在密切关系,尤其在调控乙肝病毒介导的肝癌、人乳头瘤病毒介导的宫颈癌及EB病毒介导的鼻咽癌、淋巴瘤等肿瘤中发挥重要作用。在病毒导致肿瘤的发生与发展过程中,miRNA表达谱出现时间与空间上的改变,其表达调控成为近年来病毒致癌的研究热点。我们简要综述病毒致癌相关mi RNA的研究进展。     

环状RNA的功能特性与胃癌的发生及诊断

环状RNA(circular RNA, circRNA)是一类具备环状闭合结构的内源性非编码RNA(nocoding RNA,ncRNA),主要由外显子和(或)内含子转录而成,具有组织和细胞表型特异性及稳定性,在生命活动中行使着重要的生物学功能,如circRNA可充当微小RNA(microRNA, miRNA)海绵以调控基因表达、与蛋白质相互作用、直接参与翻译过程、参与免疫反应、调控细胞功能、参与缺氧诱导肿瘤发生发展等功能。特别是参与肿瘤的发生发展使circRNA能成为肿瘤诊断及治疗的潜在靶点。本文将从circRNA的功能、参与胃癌的发生发展以及作为临床诊断标志物等展开综述。     

环状RNA与病毒感染之间相互关系的研究进展

非编码RNA (non-coding RNA,ncRNA)是指一类不具有编码蛋白质功能的RNA,包括转运RNA (transfer RNA,tRNA)、核糖体RNA (ribosomal RNA,rRNA)、微小RNA (micro RNA,miRNA)、长链非编码RNA (long non-coding RNA,lncRNA)以及环状RNA(circular RNA,circRNA)等.近年来circRNA在癌症,肿瘤以及心脑血管疾病等多种疾病中被证实发挥重要作用,此外研究还发现宿主circRNA与病毒来源的cicrRNA均会参与到病毒感染进程,但其中circRNA发挥的功能还有待进一步研究,因此,该文综述了circRNA的发现、分类、主要功能以及宿主circRNA和病毒来源的circRNA与病毒感染之间相互关系的研究进展,将有助于理解circRNA与病毒感染之间的互作机制.     

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。     

小鼠正常黑素细胞和小鼠B16黑素瘤细胞的环状RNAs表达谱

黑素瘤是一种多发于皮肤的恶性肿瘤,因其侵袭性强,预后差等特点一直是科研人员关注的热点。环状RNAs(circRNAs)是一种新型内源性非编码RNA,广泛参与动物生长发育、细胞分化和信号转导等生理过程,但circRNAs在黑素瘤细胞内的分子机制尚未被充分解析。本研究以小鼠(C57BL/6J)正常黑素细胞及B16黑素瘤细胞为研究对象,采用二代测序技术分析两种细胞间circRNAs表达特性。测序结果显示,小鼠正常黑素细胞和黑素瘤细胞中共有851个circRNAs,其中195个差异表达circRNAs(DECs)。GO及KEGG数据库注释发现,DECs的来源基因主要参与细胞周期(cell cycle)、紧密结合(tight junction)、Rap1信号通路(Rap1 signaling pathway)、TGF-beta信号通路(TGF-beta signaling pathway)等与细胞增殖、迁移相关的信号通路;探究发现,黑素瘤细胞中显著性高表达的circE2F5(circ-3:14578602|14606309)通过上调E2F5的表达促进黑素瘤细胞增殖。circRNA靶基因预测发现,...     

c-Myc-induced circ-NOTCH1 promotes aggressive phenotypes of nasopharyngeal carcinoma cells by regulating the miR-34c-5p/c-Myc axis

Nasopharyngeal carcinoma (NPC) is the subclass of head and neck cancer with the highest incidence among otolaryngology malignancies. A growing amount of evidence has proven that circular RNAs (circRNAs) play key roles in the progression of multiple cancers. It has been reported that circ-NOTCH1 is a novel circRNA and functions as an oncogene in gastric cancer, while the regulatory mechanism of circ-NOTCH1 in NPC remains unknown. In the present research, our findings revealed that circ-NOTCH1 was overexpressed in NPC tissues and cells. Circ-NOTCH1 knockdown suppressed NPC cell proliferation, invasion, and migration. Subsequently, we discovered that c-Myc can activate circ-NOTCH1 by binding to the NOTCH1 promoter. c-Myc functioned as a tumor promoter in NPC cells. Mechanistically, circ-NOTCH1 served as a competitive endogenous RNA to modulate c-Myc expression by sponging miR-34c-5p. Additionally, overexpression of c-Myc reversed the circ-NOTCH1 knockdown-mediated inhibition of NPC cellular progression. Overall, this study suggested that c-Myc-induced circ-NOTCH1 promoted malignant phenotypes of NPC cells by regulating the miR-34c-5p/c-Myc axis.     

High NEK2 confers to poor prognosis and contributes to cisplatin-based chemotherapy resistance in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and Southeast Asia, but the molecular mechanism of its pathogenesis is poorly understood. Our previous work demonstrated that NEK2 is overexpressed in multiple cancers. However, how NEK2 involves in NPC development remains to be elucidated. In this study, we firstly identified NEK2, located at +1q32-q33, a late event in NPC pathogenesis, overexpressed in the stage III-IV and paired sequential recurrent patients with NPC by immunohistochemistry. Furthermore, Kaplan-Meier analysis indicated high NEK2 conferred an inferior overall survival in NPC. In addition, cisplatin experiments with cell counting kit-8, colony formation, and a xenograft mice model of NPC demonstrated that NEK2 contributed to proliferation and cisplatin resistance in vitro and in vivo. On the contrary, downregulation of NEK2 by short hairpin RNA inhibited NPC cell growth and increased the sensitivity of cisplatin treatment in vitro. Thus, increased expression of NEK2 protein could not be predicted for poor survival but used as a novel biomarker for recurrence of NPC. Targeting NEK2 has the potential to eradicate the cisplatin-based chemotherapy resistant NPC cells.     

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。     

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.     

环状RNA：胃癌诊治的新星

环状RNA (circular RNA,circRNA)是一类闭合环状结构的RNA分子，广泛分布于各种组织中，它比线性RNA更稳定。circRNA分为外显子circRNA、外显子-内含子circRNA和内含子circRNA等3类。circRNA的主要功能为充当微RNA海绵、与RNA结合蛋白结合、翻译成蛋白质和调节转录等。近年来，大量研究表明，circRNA的异常表达在胃癌发生发展过程中起着至关重要的作用。circPTPN22、hsa＿circ＿0001772、circCYFIP2、hsa＿circ＿0017639和circPIP5K1A等的上调以及hsa＿circ＿002059、hsa＿circ＿0000190和circMTO1等的下调与胃癌的增殖和转移密切相关；而hsa＿circ＿0001313等影响胃癌细胞的顺铂耐药性。组织、血浆及外泌体中circPTPN22、hsa＿circ＿102958、hsa＿circ＿0141633、hsa＿circ＿0065149和hsa＿circ＿0026344等是胃癌新型诊断标志物；而hsa＿circ＿0005529、circ-RanGAP1、cir...     

CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms

A circRNA is a type of endogenous noncoding RNA that consists of a closed circular RNA molecule formed by reverse splicing; these RNAs are widely distributed in a variety of biological cells. In contrast to linear RNAs, circRNAs have no 5′ cap or 3′ poly(A) tail. They have a stable structure, a high degree of conservation, and high stability, and they are richly and specifically expressed in certain tissues and developmental stages. CircRNAs play a very important role in the occurrence and progression of malignant tumors. According to their origins, circRNAs can be divided into four types: exon-derived circRNAs (ecRNAs), intron-derived circRNAs (ciRNAs), circRNAs containing both exons and introns (EIciRNAs) and intergenic circRNAs. A large number of studies have shown that circRNAs have a variety of biological functions, participate in the regulation of gene expression and play an important role in the occurrence and progression of tumors. In this paper, the structure and function of circRNAs are reviewed, along with their biological role in malignant tumors of the digestive tract, in order to provide a reference for the diagnosis and treatment of digestive system neoplasms.Subject terms: Tumour biomarkers, Non-coding RNAs     

YKL-40在脑胶质母细胞瘤微环境中的作用

胶质母细胞瘤是大脑及其他中枢神经系统最常见的恶性肿瘤,其复杂的肿瘤微环境是胶质母细胞瘤临床治疗的主要挑战,也是胶质母细胞瘤患者复发率高、生存率低的主要原因。YKL-40,这一分泌性蛋白质与多种类型的癌症预后不良相关,且在高级别胶质瘤尤其是胶质母细胞瘤患者中血清水平与肿瘤组织表达水平显著升高,而在低级别胶质瘤中并未发现这一特征。这提示,YKL-40与胶质瘤分级及胶质母细胞瘤恶性发展过程密切相关。针对YKL-40的抗体治疗也被证明能够与电离辐射协同抑制胶质母细胞瘤血管生成及恶性发展。基于YKL-40的临床价值,本文将从肿瘤微环境的角度,归纳总结YKL-40在恶性肿瘤中的相关研究成果,并讨论其在胶质母细胞瘤发生发展中的相关作用及临床应用前景。