Circular RNA(circRNA)is a novel type of endogenous non-coding RNA.Most circRNAs act as microRNA(miRNA)sponges to regulate the expression of functional genes.In addition,some circRNAs can be translated and interact with RNA-binding proteins to perform biological functions.The expression of circRNAs is prevalent in tissues and body fluids,and their abnormal expression is related to tumor progression.circRNAs are stable even under the treatment of RNase R because of their circular conformation.As circRNAs have construct stability,wide variety,specific regulation of tumor progression and high expression in body fluids,it is potential for circRNAs to serve as candidate diagnostic,prognostic and therapeutic targets.However,the knowledge about circRNAs remains poor.In addition to the not completely resolved functions and generation mechanisms of circRNAs,the annotations of circRNAs are also waiting for expanding.Here,we review the generation mechanisms,biological functions,and application of circRNAs in tumor research,aiming to provide integrated information for the future research.
Biomarkers, Tumor/genetics* ; MicroRNAs ; Prognosis ; RNA, Circular

INTRODUCTION: Sepsis is defined as a life-threatening complication that occurs when the body responds to an infection attacking the host. Sepsis rapidly progresses and patients deteriorate and develop septic shock, with multiple organ failure, if not promptly treated. Currently no effective therapy is available for sepsis; therefore, early diagnosis is crucial to decrease the high mortality rate. Genome-wide expression analyses of patients in critical conditions have confirmed that the expression levels of the majority of genes are changed, suggesting that the molecular basis of sepsis is at the gene level. This review aims to elucidate the role of circular (circ) RNAs in the pathogenesis of sepsis and sepsis-induced organ damage. In addition, the feasibility of using circRNAs as novel diagnostic biomarkers for sepsis is also discussed, as well as circRNA-based therapy. METHOD: This narrative review is based on a literature search using Medline database. Search terms used were "circular RNAs and sepsis", "circRNAs and sepsis", "non-coding RNAs and sepsis", "ncRNAs and sepsis", "circRNAs and septic pathogenesis", "circRNAs and septic model", "circRNAs and septic shock" and "circRNAs, biomarker, and sepsis". RESULTS: Numerous studies indicate that circRNAs might exert pivotal roles in regulating the immune system of the host against various pathogens, such as bacteria and viruses. Dysregulation of circRNA expression levels has been confirmed as an early event in sepsis and associated with the inflammatory response, immunosuppression and coagulation dysfunction. This impairment in regulation eventually leads to multiple organ dysfunctions, including of the kidneys, lungs and heart. CONCLUSION By investigating the regulation of circRNAs in sepsis, new molecular targets for the diagnosis and intervention of sepsis can be identified. Such an understanding will be important for the development of therapeutic drugs.
Biomarkers ; Humans ; RNA, Circular ; Shock, Septic/genetics*

Objective Circular RNAs (circRNAs) are non-coding RNAs (ncRNA) circularized without a 3' polyadenylation [poly-(A)] tail or a 5' cap, resulting in a covalently closed loop structure. circRNAs were first discovered in RNA viruses in the 1970s, but only a small number of circRNAs were discovered at that time due to limitations in traditional polyadenylated transcriptome analyses. With the development of specific biochemical and computational methods, recent studies have shown the presence of abundant circRNAs in eukaryotic transcriptomes. circRNAs play vital roles in many physiological and pathological processes, such as acting as miRNA sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and even serving as translation templates. Current evidence has shown that circRNAs can be potentially used as excellent biomarkers for diagnosis, therapeutic effect evaluation, and prognostic assessment of a variety of diseases, and they may also provide effective therapeutic targets due to their stability and tissue and development-stage specificity. This review focuses on the properties of circRNAs and their immune relationship to disease, and explores the role of circRNAs in immune-related diseases and the directions of future research.
Biomarkers ; MicroRNAs/genetics* ; RNA, Circular ; Transcriptome

Circular RNAs (circRNAs),a group of highly conserved small RNAs,are characterized by a closed circular structure from precursor linear RNA through reverse splicing.They are powerful regulators of the physiological and pathological processes in organisms at different development stages.Zebrafish can be used for the high-throughput drug screening with low cost.Thus,the circRNAs associated with development and inflammation can be mined from zebrafish.Recently,a variety of circRNAs in zebrafish have been identified and characterized.Studies have proved that circRNAs play a vital role in the development and inflammation of zebrafish.The paper summarizes the classification,characteristics,and biological functions of circRNAs,and reviews the research progress in zebrafish's circRNAs.
Animals ; Inflammation ; RNA/genetics* ; RNA, Circular ; Zebrafish/genetics*

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.
Humans ; RNA, Circular ; MicroRNAs/genetics* ; Neoplasms ; Hematologic Neoplasms/genetics* ; Biomarkers

Metastases account for the overwhelming majority of cancer-associated deaths. The dissemination of cancer cells from the primary tumor to distant organs involves a complex process known as the invasion-metastasis cascade. The underlying biological mechanisms of metastasis, however, remain largely elusive. Recently, the discovery and characterization of non-coding RNAs (ncRNAs) have revealed the diversity of their regulatory roles, especially as key contributors throughout the metastatic cascade. Here, we review recent progress in how three major types of ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) are involved in the multistep procedure of metastasis. We further examine interactions among the three ncRNAs as well as current progress in their regulatory mechanisms. We also propose the prevention of metastasis in the early stages of cancer progression and discuss current translational studies using ncRNAs as targets for metastasis diagnosis and treatments. These studies provide insights into developing more effective strategies to target metastatic relapse.
Gene Expression Regulation, Neoplastic/genetics* ; RNA, Untranslated/genetics* ; MicroRNAs ; RNA, Long Noncoding ; RNA, Circular/genetics*

Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.
Bees/genetics* ; Animals ; Larva/metabolism* ; RNA, Circular/genetics* ; RNA, Small Interfering/genetics* ; MicroRNAs/genetics*

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal-fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.
Pregnancy ; Female ; Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; RNA, Circular/genetics* ; Trophoblasts ; Pregnancy Complications/genetics*

Parasite-derived non-coding RNAs (ncRNAs) not only contribute to life activities of parasites, and microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) may generate a competitive endogenous RNA (ceRNA) regulatory network with host miRNAs and mRNAs via extracellular vesicles, thereby participating in infection and pathogenic processes. This article presents an overview of characterizing ncRNAs derived from parasites and the cross-species regulatory role of parasite-derived ncRNAs in host gene expression and its underlying mechanisms.
Animals ; Parasites ; Gene Regulatory Networks ; MicroRNAs/metabolism* ; RNA, Messenger/genetics* ; RNA, Circular/genetics* ; RNA, Competitive Endogenous

Circular RNA (circRNA) is a single-stranded circular closed RNA molecule formed from linear RNA through reverse splicing. circRNAs are stable, highly conserved, and tissue-specific. circRNAs can regulate physiological and pathological processes through various mechanisms such as formation of competing endogenous RNA and interaction with binding proteins. It has been recently revealed that circRNAs can be translated into peptides and proteins to participate in the initiation and development of cancer. circRNAs are promising diagnostic and prognostic markers for human cancers as well as potential drug targets for cancer therapy. This review summarized the research progresses related to circRNA-encoded peptides and proteins in a variety of cancers. These peptides and proteins are translated through two different mechanisms that depend on internal ribosome entry site and m6A, respectively. We also summarized the potential use of circRNA-encoded peptides and proteins in the diagnosis, treatment, prognosis and mechanistic studies of various cancers.
Humans ; Internal Ribosome Entry Sites ; Neoplasms/genetics* ; Peptides, Cyclic ; RNA/genetics* ; RNA, Circular/genetics*