A Novel Intronic Circular RNA Antagonizes Influenza Virus by Absorbing a microRNA That Degrades CREBBP and Accelerating IFN-β Production

Circular RNAs (circRNAs) are new members of the long noncoding RNA families and have been identified in a variety of organisms, including plants, animals, and humans. Accumulating data indicate that circRNAs perform multiple functions in a variety of cellular processes associated with human diseases, such as Alzheimer’s disease and cancer; however, the roles of circRNAs in virus infection have been largely uninvestigated.

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Implication of regulatory networks of long noncoding RNA/circular RNA-miRNA-mRNA in diabetic cardiovascular diseases

Epigenomics ◽

10.2217/epi-2020-0188 ◽

2020 ◽

Vol 12 (21) ◽

pp. 1929-1947

Author(s):

Wei Xiong ◽

Mengran Yao ◽

Yuqiao Yang ◽

Yan Qu ◽

Jinqiao Qian

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Diseases ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Regulatory Networks ◽

Noncoding Rnas ◽

Circular Rna ◽

Competing Endogenous Rna ◽

Prognostic Evaluation ◽

Functional Roles

Diabetic cardiovascular diseases (DCVDs) are the most common complications of diabetes mellitus and are considered to be one of the most important threats to global health and an economic burden. Long noncoding RNA (lncRNA), circular RNA (circRNA), and miRNA are a novel group of noncoding RNAs that are involved in the regulation of various pathophysiological processes, including DCVDs. Interestingly, both lncRNA and circRNA can act as competing endogenous RNA of miRNA, thereby regulating the expression of the target mRNA by decoying or sponging the miRNA. In this review, we focus on the mechanistic, pathological and functional roles of lncRNA/circRNA-miRNA-mRNA networks in DCVDs and further discuss the potential implications for early detection, therapeutic intervention and prognostic evaluation.

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Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2014/780521 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Guangbing Li ◽

Haohai Zhang ◽

Xueshuai Wan ◽

Xiaobo Yang ◽

Chengpei Zhu ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Comprehensive Review ◽

Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

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Circular RNAs in Cardiovascular Disease: An Overview

BioMed Research International ◽

10.1155/2017/5135781 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 66

Author(s):

Ximin Fan ◽

Xinyu Weng ◽

Yifan Zhao ◽

Wei Chen ◽

Tianyi Gan ◽

...

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Noncoding Rna ◽

Essential Role ◽

Closed Loop ◽

Regulation Of Gene Expression ◽

Circular Rna ◽

Circular Rnas ◽

Mirna Sponges

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

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Circular RNA Expression Profile of Pancreatic Ductal Adenocarcinoma Revealed by Microarray

Cellular Physiology and Biochemistry ◽

10.1159/000453186 ◽

2016 ◽

Vol 40 (6) ◽

pp. 1334-1344 ◽

Cited By ~ 57

Author(s):

Haimin Li ◽

Xiaokun Hao ◽

Huimin Wang ◽

Zhengcai Liu ◽

Yong He ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Expression Profile ◽

Mammalian Cells ◽

Noncoding Rna ◽

Circular Rna ◽

Pathological Process ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

Normal Tissues ◽

Polymerase Chain

Background/Aims: Circular RNAs (circRNAs) are a special novel type of a stable, diverse and conserved noncoding RNA in mammalian cells. Particularly in cancer, circRNAs have been reported to be widely involved in the physiological/pathological process of life. However, it is unclear whether circRNAs are specifically involved in pancreatic ductal adenocarcinoma (PDAC). Methods: We investigated the expression profile of circRNAs in six PDAC cancer samples and paired adjacent normal tissues using microarray. A high-throughput circRNA microarray was used to identify dysregulated circular RNAs in six PDAC patients. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. Results: We revealed and confirmed that a number of circRNAs were dysregulated, which suggests a potential role in pancreatic cancer. Conclusions: this study demonstrates that clusters of circRNAs are aberrantly expressed in PDAC compared with normal samples and provides new potential targets for the future treatment of PDAC and novel insights into PDAC biology.

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The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers

Nucleic Acids Research ◽

10.1093/nar/gkaa1119 ◽

2020 ◽

Vol 48 (22) ◽

pp. 12618-12631

Author(s):

Mengbiao Guo ◽

Zhen-Dong Xiao ◽

Zhiming Dai ◽

Ling Zhu ◽

Hang Lei ◽

...

Keyword(s):

Cancer Progression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Chimeric Proteins ◽

Protein Coding ◽

Cellular Processes ◽

Cancer Types ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Somatic Copy Number Alterations

Abstract The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B–G039927 and EPS15L1–lncOR7C2–1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.

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Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

Cardiovascular Therapeutics ◽

10.1155/2020/2016259 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Guang Yang ◽

Chunsheng Lin

Keyword(s):

Heart Failure ◽

Cell Apoptosis ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Heart Diseases ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cellular Processes ◽

Wide Range

Background. Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods. Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results. We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions. Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

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A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain

10.1101/279687 ◽

2018 ◽

Cited By ~ 1

Author(s):

Benjamin Kleaveland ◽

Charlie Y. Shi ◽

Joanna Stefano ◽

David P. Bartel

Keyword(s):

Long Noncoding Rna ◽

Regulatory Network ◽

Noncoding Rna ◽

Gene Editing ◽

Noncoding Rnas ◽

Circular Rna ◽

Mammalian Brain ◽

Viral Rnas ◽

Gene Regulatory ◽

Regulatory Rnas

SUMMARYNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.HIGHLIGHTSA long noncoding RNA, a circular RNA, and two microRNAs form a regulatory networkThe Cyrano long noncoding RNA directs potent, multiple-turnover destruction of miR-7Unchecked miR-7 prevents accumulation of Cdr1as circular RNA in cytoplasm of neurons miR-7 prevents this accumulation by enhancing the miR-671-directed slicing of Cdr1as

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ceRNA Cross-Talk in Paulownia Witches’ Broom Disease

International Journal of Molecular Sciences ◽

10.3390/ijms19082463 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2463

Author(s):

Guoqiang Fan ◽

Zhe Wang ◽

Xiaoqiao Zhai ◽

Yabing Cao

Keyword(s):

Rna Sequencing ◽

Molecular Mechanism ◽

Cross Talk ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Circular Rna ◽

Differentially Expressed ◽

Competing Endogenous Rna ◽

Broom Disease ◽

Insight Into

Long noncoding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) are important in the regulation of life activities. However, their function is unclear in Paulownia fortunei. To identify lncRNAs, circRNAs, and miRNA, and investigate their roles in the infection progress of Paulownia witches’ broom (PaWB) disease, we performed RNA sequencing of healthy and infected P. fortunei. A total of 3126 lncRNAs, 1634 circRNAs, and 550 miRNAs were identified. Among them, 229 lncRNAs, 65 circRNAs, and 65 miRNAs were differentially expressed in a significant manner. We constructed a competing endogenous RNA (ceRNA) network, which contains 5 miRNAs, 4 circRNAs, 5 lncRNAs, and 15 mRNAs, all of which were differentially expressed between healthy and infected P. fortunei. This study provides the first catalog of candidate ceRNAs in Paulownia and gives a revealing insight into the molecular mechanism responsible for PaWB.

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Expanding uncapped translation and emerging function of circular RNA in carcinomas and noncarcinomas

Molecular Cancer ◽

10.1186/s12943-021-01484-7 ◽

2022 ◽

Vol 21 (1) ◽

Author(s):

Yan Wang ◽

Chunjie Wu ◽

Yu Du ◽

Zhongwei Li ◽

Minle Li ◽

...

Keyword(s):

Internal Ribosome Entry Site ◽

Therapeutic Potential ◽

Circular Rna ◽

Human Diseases ◽

Circular Rnas ◽

Host Proteins ◽

Entry Site ◽

Internal Ribosome Entry ◽

Polysome Profiling ◽

Translation Mechanism

AbstractCircular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5’ end cap and a 3’ end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.

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