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。     

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.     

环状RNA的生物学功能及其在肿瘤发生中的作用

近年来,随着RNA研究技术的进步,研究者们在多种生物中发现了数量众多的环状RNA,且发现它们具有重要的生物学功能。环状RNA来源于内含子或外显子,可以充当微小RNA海绵,还能与蛋白质相结合,从而参与基因表达调控并影响蛋白质的功能,此外,个别环状RNA甚至能编码蛋白质。更重要的是,环状RNA在肿瘤(如:胃癌、肝癌、结直肠癌、乳腺癌、宫颈癌和卵巢癌等)的发生和发展过程中起着重要的调控作用。因此,环状RNA有希望成为肿瘤诊断的标志物和治疗的新靶点。     

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.     

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。     

The emerging function and clinical significance of circRNAs in Thyroid Cancer and Autoimmune Thyroid Diseases

Thyroid cancer (TC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide. The incidence of TC, especially that of papillary thyroid carcinoma (PTC); has increased rapidly in recent decades. Autoimmune thyroid disease (AITD) is closely related to TC and has an estimated prevalence of 5%. Thus, it is becoming increasingly important to identify potential diagnostic biomarkers and therapeutic targets for TC and AITD. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently bonded circular structures that lack 5''-3'' polarity and polyadenylated tails. Several circRNAs play crucial roles in the development of various diseases, including TC and AITD, and could be important new biomarkers and/or targets for the diagnosis and therapy of such disorders. Although there are four subtypes of TC, research on circRNA has largely focused on its connection to PTC. Therefore, this review mainly summarizes the relationships between circRNAs and PTC and AITD, including the molecular mechanisms underlying these relationships. In particular, the functions of “miRNA sponges” and their interactions with proteins and RNA are discussed. The possible targeting of circRNAs for the prevention, diagnosis, and treatment of TC and AITD is also described. CircRNAs could be potential biomarkers of TC and AITD, although validation will be required before they can be implemented in clinical practice.     

CircKIF2A contributes to cell proliferation,migration, invasion and glycolysis in human neuroblastoma by regulating miR-129-5p/PLK4 axis

Molecular and Cellular Biochemistry - Multiple circular RNAs (circRNAs) have been identified to act as essential mediators in diverse human cancers. However, the roles of circRNAs in neuroblastoma...     

Newly discovered mechanisms that mediate tumorigenesis and tumour progression: circRNA-encoded proteins

Proteins produced by cap-independent translation mediated by an internal ribosome entry site (IRES) in circular RNAs (circRNAs) play important roles in tumour progression. To date, numerous studies have been performed on circRNAs and the proteins they encode. In this review, we summarize the biogenesis of circRNAs and the mechanisms regulating circRNA-encoded proteins expression. We also describe relevant research methods and their applications to biological processes such as tumour cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), apoptosis, autophagy and chemoresistance. This paper offers deeper insights into the roles that circRNA-encoded proteins play in tumours. It also provides a theoretical basis for the use of circRNA-encoded proteins as biomarkers of tumorigenesis and for the development of new targets for tumour therapy.     

circRNAs在成骨细胞分化中的调控作用

环状RNAs(circular RNAs,circRNAs)是一类新型内源性非编码RNAs,在调节生长发育、疾病发展等方面具有重要的生物学功能。新近研究证实,circRNAs参与调控牙周膜干细胞和骨髓干细胞等的成骨细胞分化。该文就当前circRNAs在成骨细胞分化中的最新研究进展作一综述,以帮助开发骨科疾病新疗法。     

Prospect of circular RNA in osteogenesis: A novel orchestrator of signaling pathways

Circular RNAs (circRNAs) were initially regarded as by-products of aberrant splicing. But now, there are substantial evidence on their various roles in the regulation of genes during the development of organs and diseases. Consistent with these breakthroughs, it is experiencing rapid growth that circRNAs function as the important checkpoints during the osteogenesis. Therefore, characterizing the roles of circRNAs is useful and critical to better understanding the process of osteogenic differentiation, which could provide new avenues for the diagnosis and treatment of bone diseases, such as bone defects and osteoporosis. In this review, we presented a map of the interaction between circRNAs and the molecules of signaling pathways associated with osteogenesis, summarized the current knowledge of the biological functions of circRNAs during the osteogenic differentiation, figured out the limits of existing research works, and provided a novel look on the diagnostic and therapeutic methods of bone diseases based on circRNAs.     

circ-ZNF609: A potent circRNA in human cancers

Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.     

Regulatory non‐coding RNAs in acute myocardial infarction

Acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that leads to high mortality and morbidity globally. Various therapeutic targets for AMI have been investigated in recent years, including the non‐coding RNAs (ncRNAs). NcRNAs, a class of RNA molecules that typically do not code proteins, are divided into several subgroups. Among them, microRNAs (miRNAs) are widely studied for their modulation of several pathological aspects of AMI, including cardiomyocyte apoptosis, inflammation, angiogenesis and fibrosis. It has emerged that long ncRNAs (lncRNAs) and circular RNAs (circRNAs) also regulate these processes via interesting mechanisms. However, the regulatory functions of ncRNAs in AMI and their underlying functional mechanisms have not been systematically described. In this review, we summarize the recent findings involving ncRNA actions in AMI and briefly describe the novel mechanisms of these ncRNAs, highlighting their potential application as therapeutic targets in AMI.     

环RNA研究概况

在1976年就已经发现RNA可以具有环形形式。但是长期以来对环形RNA(circRNAs)主要是作为一些特例加以研究。随着高通量RNA测序技术以及生物信息学的发展,近几年的研究发现circRNAs在真核生物中普遍存在,并且具有一定的保守性和细胞特异性。越来越多的证据指明circRNAs不是剪切噪音,而是具有一定生物学功能,可能与一系列调控甚至疾病的发生和发展相关。     

Emerging functions of piwi-interacting RNAs in diseases

PIWI-interacting RNAs (piRNAs) are recently discovered small non-coding RNAs consisting of 24-35 nucleotides, usually including a characteristic 5-terminal uridine and an adenosine at position 10. PIWI proteins can specifically bind to the unique structure of the 3′ end of piRNAs. In the past, it was thought that piRNAs existed only in the reproductive system, but recently, it was reported that piRNAs are also expressed in several other human tissues with tissue specificity. Growing evidence shows that piRNAs and PIWI proteins are abnormally expressed in various diseases, including cancers, neurodegenerative diseases and ageing, and may be potential biomarkers and therapeutic targets. This review aims to discuss the current research status regarding piRNA biogenetic processes, functions, mechanisms and emerging roles in various diseases.     

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.     

The emerging roles of circular RNAs in regulating the fate of stem cells

Circular RNAs(circRNAs) are a large family of RNAs shaping covalently closed ring-like molecules and have become a hotspot with thousands of newly published studies. Stem cells are undifferentiated cells and have great potential in medical treatment due to their self-renewal ability and differentiation capacity. Abundant researches have unveiled that circRNAs have unique expression profile during the differentiation of stem cells and could serve as promising biomarkers of these cells. There are key circRNAs relevant to the differentiation, proliferation, and apoptosis of stem cells with certain mechanisms such as sponging miRNAs, interacting with proteins, and interfering mRNA translation. Moreover, several circRNAs have joined in the interplay between stem cells and lymphocytes. Our review will shed lights on the emerging roles of circRNAs in regulating the fate of diverse stem cells.