scholarly journals Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Min ◽  
Dong-liang Liu ◽  
Xing-dong Xiong
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Suppressive Effect ◽  
Cerebrovascular Diseases ◽  
Circular Rnas ◽  
Clinical Implications ◽  
Future Directions ◽  
Rna Molecules ◽  
Competing Endogenous Rnas

Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

scholarly journals CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1956
Author(s):  
Francesco Manfrevola ◽  
Bruno Ferraro ◽  
Carolina Sellitto ◽  
Domenico Rocco ◽  
Silvia Fasano ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Molecular Mechanisms ◽  
Gradient Centrifugation ◽  
Circular Rnas ◽  
Amino Acid Supplementation ◽  
Differential Analysis ◽  
Mrna Targets ◽  
Motility Regulation ◽  
Quantitative Changes

The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of CRISP2, CATSPER1 and PATE1 mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.

scholarly journals The Role of Circular RNAs in Keratinocyte Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4240
Author(s):  
Thomas Meyer ◽  
Michael Sand ◽  
Lutz Schmitz ◽  
Eggert Stockfleth
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Factors Associated ◽  
New Therapeutic Approaches ◽  
Non Coding Rna ◽  
Micro Rnas ◽  
Pubmed Search

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

scholarly journals Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 27 ◽  
Author(s):  
Dominik A. Barth ◽  
Felix Prinz ◽  
Julia Teppan ◽  
Katharina Jonas ◽  
Christiane Klec ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Protein Coding ◽  
Rna Molecules ◽  
Von Hippel Lindau ◽  
Hypoxic Conditions ◽  
Main Regulator ◽  
Upstream Regulators

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer. Besides hypoxia, cancer cells may promote HIF expression under normoxic conditions by altering various upstream regulators, cumulating in HIF upregulation and enhanced glycolysis and angiogenesis, altogether promoting tumor proliferation and progression. Therefore, understanding the underlying molecular mechanisms is crucial to discover potential future therapeutic targets to evolve cancer therapy. Long non-coding RNAs (lncRNA) are a class of non-protein coding RNA molecules with a length of over 200 nucleotides. They participate in cancer development and progression and might act as either oncogenic or tumor suppressive factors. Additionally, a growing body of evidence supports the role of lncRNAs in the hypoxic and normoxic regulation of HIF and its subunits HIF-1α and HIF-2α in cancer. This review provides a comprehensive update and overview of lncRNAs as regulators of HIFs expression and activation and discusses and highlights potential involved pathways.

scholarly journals Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

2020 ◽  
Vol 21 (5) ◽  
pp. 1798 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Edzard Schwedhelm ◽  
Hans Worthmann ◽  
Chi-un Choe
Keyword(s):  
Ischemic Stroke ◽  
Vascular Function ◽  
Cerebrovascular Diseases ◽  
Current Evidence ◽  
Clinical Implications ◽  
Pathophysiological Role ◽  
Health And Disease ◽  
Oxide Synthase ◽  
Derivatives Of

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

Competing Endogenous RNAs in Hepatocellular Carcinoma—The Pinnacle of Rivalry

2019 ◽  
Vol 39 (04) ◽  
pp. 463-475 ◽  
Author(s):  
Abdelrahman Yousry Afify ◽  
Salma Abdulmaqsoud Ibrahim ◽  
Mennah Hisham Aldamsisi ◽  
Mai Saad Zaghloul ◽  
Nada El-Ekiaby ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Solo Performance ◽  
Regulatory Pathways ◽  
Small Noncoding Rnas ◽  
Posttranscriptional Gene Regulation ◽  
Competing Endogenous Rnas ◽  
Genomic Regulation

AbstractThe role of noncoding transcripts in gene expression is nowadays acknowledged to keep various diseases at bay—despite being referred to as “junk” DNA several years ago. Believed to be at the heart of multiple regulatory pathways, microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in posttranscriptional gene regulation. Recently, the discovery of ncRNAs that compete for shared miRNA pools has dimmed the light on the solo performance of miRNAs in genomic regulation. Indeed, several studies describe RNAs such as long noncoding RNAs, mRNAs, circular RNAs, pseudogenes, and viral RNAs as competing endogenous RNAs (ceRNAs) that sequester miRNAs, allowing for de-repression of downstream miRNA targets. Such integration between coding and noncoding transcripts forms complex ceRNA networks that when dysregulated lead to several diseases such as hepatocellular carcinoma. Here, the authors review perturbed ceRNA networks in hepatocellular carcinoma, describe the role of each in tumorigenesis, and discuss their various clinical implications.

scholarly journals circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

2020 ◽  
Author(s):  
Qin Xu ◽  
Bo Deng ◽  
Manlin Li ◽  
Yang Chen ◽  
Li Zhuan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Competing Endogenous Rnas ◽  
Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

scholarly journals N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Wu ◽  
Xin Guo ◽  
Yi Wen ◽  
Shangqing Huang ◽  
Xiaohui Yuan ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Circular Rna ◽  
Regulatory Mechanisms ◽  
Circular Rnas ◽  
Biological Functions ◽  
Future Directions ◽  
Rna Molecules ◽  
Physiological Processes ◽  
Rna Biology ◽  
Insight Into

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

scholarly journals The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyao Hu ◽  
Hua Zhu ◽  
Yang Shen ◽  
Xiaoyu Zhang ◽  
Xiaoqin He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Circular Rnas ◽  
First Line ◽  
Advanced Hcc ◽  
Chemotherapy Agent ◽  
Development Of Resistance ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

scholarly journals Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Yanshuo Han ◽  
Hao Zhang ◽  
Ce Bian ◽  
Chen Chen ◽  
Simei Tu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Human Life ◽  
Abdominal Aortic Aneurysms ◽  
Circular Rna ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Circular Rnas ◽  
Regulatory Pathways ◽  
Abdominal Aortic

Abdominal aortic aneurysms (AAAs) have posed a great threat to human life, and the necessity of its monitoring and treatment is decided by symptomatology and/or the aneurysm size. Accumulating evidence suggests that circular RNAs (circRNAs) contribute a part to the pathogenesis of AAAs. circRNAs are novel single-stranded RNAs with a closed loop structure and high stability, having become the candidate biomarkers for numerous kinds of human disorders. Besides, circRNAs act as molecular “sponge” in organisms, capable of regulating the transcription level. Here, we characterize that the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. In the present work, studies on the biosynthesis, bibliometrics, and mechanisms of action of circRNAs were aims comprehensively reviewed, the role of circRNAs in the AAA pathogenic mechanism was illustrated, and their potential in diagnosing AAAs was examined. Moreover, the current evidence about the effects of circRNAs on AAA development through modulating endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) was summarized. Through thorough investigation, the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. The results demonstrated that circRNAs had the application potential in the diagnosis and prevention of AAAs in clinical practice. The study of circRNA regulatory pathways would be of great assistance to the etiologic research of AAAs.

scholarly journals Integrative Analysis of CircRNA Expression and Associated ceRNA Network in Graves’ Disease

2021 ◽  
Author(s):  
Zhengrong Jiang ◽  
Linghong Huang ◽  
Lijun Chen ◽  
Jingxiong Zhou ◽  
Xuefeng Bai ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Family Members ◽  
Circular Rnas ◽  
Newly Diagnosed ◽  
Autoimmune Thyroid ◽  
Competing Endogenous Rnas ◽  
Healthy Control ◽  
Polymerase Chain ◽  
Comprehensive Study

Abstract ObjectiveGraves’ disease (GD) is the most common subtype of autoimmune thyroid disease which have the involvement of circular RNAs (circRNAs) in the pathogenesis. However, it is largely unknown about the role of circRNAs in GD. In present study, we performed a comprehensive study of the circRNAs in GD by bioinformatics analyses.MethodsCircRNAs were detected in plasma of 3 newly diagnosed GD patients and 3 healthy controls. We selected 2 up-regulated and 1 down-regulated circRNAs with different expression in GD for validation by transcriptase-quantitative polymerase chain reaction in both GD and healthy control subjects. The GTRD base was used for predicting the transcript factors of the different expression of circRNAs. Then the competing endogenous RNAs(ceRNAs) network was assembled and the analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed to predict the functions of different expression of circRNAs.ResultsA total of 366 different expression of circRNAs were detected in GD. The exonic circRNA hsa_circ_0090364 was validated as an up-regulated molecule in GD. 82 transcript factors in promoter region for hsa_circ_0090364 were predicted. The ceRNAs network revealed that the miR-378 family members acted as the target microRNAs of hsa_circ_0090364 and its downstream genes, and also unveiled the involvement of hsa_circ_0090364 in pathogenesis of GD.ConclusionsHsa_circ_0090364 might play a role of ceRNA through sponging up miR-378 family members, which demonstrated that circRNAs had an effect on regulation in GD.

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