scholarly journals Deep Characterization of Circular RNAs from Human Cardiovascular Cell Models and Cardiac Tissue

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1616
Author(s):  
Tobias Jakobi ◽  
Dominik Siede ◽  
Jessica Eschenbach ◽  
Andreas W. Heumüller ◽  
Martin Busch ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Umbilical Vein ◽  
Expression Profiles ◽  
Developed Countries ◽  
Model Systems ◽  
Start Codon ◽  
Circular Rnas ◽  
Specific Expression ◽  
Cardiac Model ◽  
Depth Analysis

For decades, cardiovascular disease (CVD) has been the leading cause of death throughout most developed countries. Several studies relate RNA splicing, and more recently also circular RNAs (circRNAs), to CVD. CircRNAs originate from linear transcripts and have been shown to exhibit tissue-specific expression profiles. Here, we present an in-depth analysis of sequence, structure, modification, and cardiac circRNA interactions. We used human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs), human healthy and diseased (ischemic cardiomyopathy, dilated cardiomyopathy) cardiac tissue, and human umbilical vein endothelial cells (HUVECs) to profile circRNAs. We identified shared circRNAs across all samples, as well as model-specific circRNA signatures. Based on these circRNAs, we identified 63 positionally conserved and expressed circRNAs in human, pig, and mouse hearts. Furthermore, we found that the sequence of circRNAs can deviate from the sequence derived from the genome sequence, an important factor in assessing potential functions. Integration of additional data yielded evidence for m6A-methylation of circRNAs, potentially linked to translation, as well as, circRNAs overlapping with potential Argonaute 2 binding sites, indicating potential association with the RISC complex. Moreover, we describe, for the first time in cardiac model systems, a sub class of circRNAs containing the start codon of their primary transcript (AUG circRNAs) and observe an enrichment for m6A-methylation for AUG circRNAs.

scholarly journals The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3250
Author(s):  
Christopher Limb ◽  
Daniel S. K. Liu ◽  
Morten T. Veno ◽  
Eleanor Rees ◽  
Jonathan Krell ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Biliary Tract ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Ductal Adenocarcinoma ◽  
Circular Rnas ◽  
Specific Expression ◽  
Biliary Tract Cancers ◽  
Cerna Network

Pancreatic Ductal Adenocarcinoma (PDAC) and biliary-tract cancers (BTC) often present at a late stage, and consequently patients have poor survival-outcomes. Circular RNAs (circRNAs) are non-coding RNA molecules whose role in tumourigenesis has recently been realised. They are stable, conserved and abundant, with tissue-specific expression profiles. Therefore, significant interest has arisen in their use as potential biomarkers for PDAC and BTC. High-throughput methods and more advanced bioinformatic techniques have enabled better profiling and progressed our understanding of how circRNAs may function in the competing endogenous RNA (ceRNA) network to influence the transcriptome in these cancers. Therefore, the aim of this systematic review was to describe the roles of circRNAs in PDAC and BTC, their potential as biomarkers, and their function in the wider ceRNA network in regulating microRNAs and the transcriptome. Medline, Embase, Scopus and PubMed were systematically reviewed to identify all the studies addressing circRNAs in PDAC and BTC. A total of 32 articles were included: 22 considering PDAC, 7 for Cholangiocarcinoma (CCA) and 3 for Gallbladder Cancer (GBC). There were no studies investigating Ampullary Cancer. Dysregulated circRNA expression was associated with features of malignancy in vitro, in vivo, and ex vivo. Overall, there have been very few PDAC and BTC tissues profiled for circRNA signatures. Therefore, whilst the current studies have demonstrated some of their functions in these cancers, further work is required to elucidate their potential role as cancer biomarkers in tissue, biofluids and biopsies.

scholarly journals Circular RNAs and Cardiovascular Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Ling Tang ◽  
Pengsheng Li ◽  
Michelle Jang ◽  
Wuqiang Zhu
Keyword(s):  
Expression Profiles ◽  
Cardiac Regeneration ◽  
Protein Translation ◽  
Heart Tissue ◽  
Circular Rnas ◽  
Specific Expression ◽  
Tissue Samples ◽  
Cardiovascular Regeneration ◽  
Mirna Sponges ◽  
Action Modes

circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.

scholarly journals Molecular interactions of miR-338 during tumor progression and metastasis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Meysam Moghbeli
Keyword(s):  
Cell Proliferation ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Main Body ◽  
Specific Expression ◽  
Aberrant Expression ◽  
Non Coding Rnas

Abstract Background Cancer, as one of the main causes of human deaths, is currently a significant global health challenge. Since the majority of cancer-related deaths are associated with late diagnosis, it is necessary to develop minimally invasive early detection markers to manage and reduce mortality rates. MicroRNAs (miRNAs), as highly conserved non-coding RNAs, target the specific mRNAs which are involved in regulation of various fundamental cellular processes such as cell proliferation, death, and signaling pathways. MiRNAs can also be regulated by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). They are highly stable in body fluids and have tumor-specific expression profiles, which suggest their suitability as efficient non-invasive diagnostic and prognostic tumor markers. Aberrant expression of miR-338 has been widely reported in different cancers. It regulates cell proliferation, migration, angiogenesis, and apoptosis in tumor cells. Main body In the present review, we have summarized all miR-338 interactions with other non-coding RNAs (ncRNAs) and associated signaling pathways to clarify the role of miR-338 during tumor progression. Conclusions It was concluded that miR-338 mainly functions as a tumor suppressor in different cancers. There were also significant associations between miR-338 and other ncRNAs in tumor cells. Moreover, miR-338 has a pivotal role during tumor progression using the regulation of WNT, MAPK, and PI3K/AKT signaling pathways. This review highlights miR-338 as a pivotal ncRNA in biology of tumor cells.

scholarly journals Lantern: an integrative repository of functional annotations for lncRNAs in the human genome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Swapna Vidhur Daulatabad ◽  
Rajneesh Srivastava ◽  
Sarath Chandra Janga
Keyword(s):  
Human Genome ◽  
Cellular Localization ◽  
Expression Profiles ◽  
Free Text ◽  
Dynamic Visualization ◽  
Specific Expression ◽  
Web Resource ◽  
Functional Dynamics ◽  
Non Coding Rnas ◽  
Retrieval Engine

Abstract Background With advancements in omics technologies, the range of biological processes where long non-coding RNAs (lncRNAs) are involved, is expanding extensively, thereby generating the need to develop lncRNA annotation resources. Although, there are a plethora of resources for annotating genes, despite the extensive corpus of lncRNA literature, the available resources with lncRNA ontology annotations are rare. Results We present a lncRNA annotation extractor and repository (Lantern), developed using PubMed’s abstract retrieval engine and NCBO’s recommender annotation system. Lantern’s annotations were benchmarked against lncRNAdb’s manually curated free text. Benchmarking analysis suggested that Lantern has a recall of 0.62 against lncRNAdb for 182 lncRNAs and precision of 0.8. Additionally, we also annotated lncRNAs with multiple omics annotations, including predicted cis-regulatory TFs, interactions with RBPs, tissue-specific expression profiles, protein co-expression networks, coding potential, sub-cellular localization, and SNPs for ~ 11,000 lncRNAs in the human genome, providing a one-stop dynamic visualization platform. Conclusions Lantern integrates a novel, accurate semi-automatic ontology annotation engine derived annotations combined with a variety of multi-omics annotations for lncRNAs, to provide a central web resource for dissecting the functional dynamics of long non-coding RNAs and to facilitate future hypothesis-driven experiments. The annotation pipeline and a web resource with current annotations for human lncRNAs are freely available on sysbio.lab.iupui.edu/lantern.

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

scholarly journals Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1155
Author(s):  
Meihui Tian ◽  
Zhipeng Cao ◽  
Hao Pang
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Early Stage ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Cardiac Damage ◽  
Postmortem Diagnosis ◽  
Specific Expression ◽  
Forensic Practice ◽  
Artery Disease

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

scholarly journals Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Dismal Prognosis ◽  
Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

scholarly journals Effects of Essential Oils-Based Supplement and Salmonella Infection on Gene Expression, Blood Parameters, Cecal Microbiome, and Egg Production in Laying Hens

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 360
Author(s):  
Georgi Yu. Laptev ◽  
Elena A. Yildirim ◽  
Larisa A. Ilina ◽  
Valentina A. Filippova ◽  
Ivan I. Kochish ◽  
...  
Keyword(s):  
Egg Production ◽  
Salmonella Enteritidis ◽  
Laying Hens ◽  
Expression Profiles ◽  
Blood Parameters ◽  
Post Inoculation ◽  
Production Traits ◽  
Immunological Parameters ◽  
Specific Expression ◽  
Blood Biochemical

One of the main roles in poultry resistance to infections caused by Salmonella is attributed to host immunity and intestinal microbiota. We conducted an experiment that involved challenging Lohmann White laying hens with Salmonella Enteritidis (SE), feeding them a diet supplemented with an EOs-based phytobiotic Intebio®. At 1 and 7 days post-inoculation, the expression profiles of eight genes related to immunity, transport of nutrients in the intestine, and metabolism were examined. Cecal microbiome composition and blood biochemical/immunological indices were also explored and egg production traits recorded. As a result, the SE challenge of laying hens and Intebio® administration had either a suppressive or activating effect on the expression level of the studied genes (e.g., IL6 and BPIFB3), the latter echoing mammalian/human tissue-specific expression. There were also effects of the pathogen challenge and phytobiotic intake on the cecal microbiome profiles and blood biochemical/immunological parameters, including those reflecting the activity of the birds’ immune systems (e.g., serum bactericidal activity, β-lysine content, and immunoglobulin levels). Significant differences between control and experimental subgroups in egg performance traits (i.e., egg weight/number/mass) were also found. The phytobiotic administration suggested a positive effect on the welfare and productivity of poultry.

scholarly journals Function of Circular RNAs in Fish and Their Potential Application as Biomarkers

2021 ◽  
Vol 22 (13) ◽  
pp. 7119
Author(s):  
Golam Rbbani ◽  
Artem Nedoluzhko ◽  
Jorge Galindo-Villegas ◽  
Jorge M. O. Fernandes
Keyword(s):  
Growth Regulation ◽  
Functional Characterization ◽  
Circular Rnas ◽  
Farmed Fish ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Taxonomic Groups ◽  
And Function

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

scholarly journals Single-Cell Expression Landscape of SARS-CoV-2 Receptor ACE2 and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1250
Author(s):  
Guangchun Han ◽  
Ansam Sinjab ◽  
Kieko Hara ◽  
Warapen Treekitkarnmongkol ◽  
Patrick Brennan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Expression Profiles ◽  
Lung Cells ◽  
Alveolar Type ◽  
Specific Expression ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Cell Expression

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.

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