scholarly journals A comprehensive profile of circulating RNAs in human serum

2017 ◽  
Author(s):  
Sinan Uğur Umu ◽  
Hilde Langseth ◽  
Cecilie Bucher-Jonannessen ◽  
Bastian Fromm ◽  
Andreas Keller ◽  
...  
Keyword(s):  
Human Serum ◽  
Population Based ◽  
Rna Seq ◽  
Serum Samples ◽  
Transfer Rnas ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Norwegian Population ◽  
Micro Rnas ◽  
Nucleolar Rnas

ABSTRACTNon-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion lllumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA). We also investigated biological and technical variation in expression, and the results suggest that many RNA molecules identified in serum contain signs of biological variation. They are therefore unlikely to be random degradation by-products. In addition, the presence of specific fragments of tRNA, snoRNA, Vault RNA and Y_RNA indicates protection from degradation. Our results suggest that many circulating RNAs in serum can be potential biomarkers.

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 Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2198
Author(s):  
Marthe Chehade ◽  
Martyn Bullock ◽  
Anthony Glover ◽  
Gyorgy Hutvagner ◽  
Stan Sidhu
Keyword(s):  
Mrna Translation ◽  
Molecular Signature ◽  
Adrenocortical Cancer ◽  
Term Survival ◽  
Rna Molecules ◽  
Clinical Biomarkers ◽  
Non Coding Rna ◽  
Micro Rnas ◽  
Complete Surgical Resection

Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics.

scholarly journals Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Biological Significance ◽  
Rna Seq ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

RNA-Seq Data Analysis Unveils Potential Conserved micro-RNAs in Agave deserti

2020 ◽  
Vol 17 ◽  
Author(s):  
Basit Jabbar ◽  
Batcho Agossa Anicet ◽  
Muhammad Bilal Sarwar ◽  
Bushra Rashid ◽  
Sameera Hassan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Abiotic Stress Tolerance ◽  
Evolutionary Relationship ◽  
Minimum Free Energy ◽  
Rna Seq ◽  
Cam Plants ◽  
Protein Coding ◽  
Rna Molecules ◽  
Micro Rnas

Aim: Exploring molecular mechanism of abiotic stress tolerance in plants is the need to overcome the deterioration of yield and quality of crop plants to meet the food security challenges of growing population. Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate target gene expression for modulating plant growth, development, and response to different stresses. Agave belonging to CAM plants’ has remarkable tolerance to extreme conditions of drought and heat; however, molecular mechanisms underlying this excellence are yet to explore. Objective: This study applies comparative genomics approach on available Transcriptome (RNA-Seq) data of Agave deserti to identify potential miRNAs, and miRNA targets. Methods: Transcriptome datasets consisting of 128,869 Agave contigs processed to create local database, for nucleotide homology analysis with 6,028 non-redundant plant miRNAs as query sequences. Protein coding sequences were removed, and potential pre-miRNA sequences were tested for stability analysis based on a variety of factors, including but not limited to %G+C content and minimum free energy (-∆G), as a filter to remove pseudo pre-miRNAs. Results: This study identified 30 unique miRNAs of Agave deserti harboring 14 different categories of precursors. Phylogenetic analysis revealed evolutionary relationship between newly identified pre-miRNAs with corresponding pre-miRNA homologues. Target genes of miRNAs predicted subsequently, and possible functions defined by functional annotation analysis. Conclusion: The results of this study will pave the way for further research, exploring the molecular mechanisms in Agave deserti and the role of miRNAs in gene regulation under abiotic stresses.

scholarly journals MicroRNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 859 ◽  
Author(s):  
Jean-François Landrier ◽  
Adel Derghal ◽  
Lourdes Mounien
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Untranslated Regions ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Micro Rnas

Metabolic disorders are characterized by the inability to properly use and/or store energy. The burdens of metabolic disease, such as obesity or diabetes, are believed to arise through a complex interplay between genetics and epigenetics predisposition, environment and nutrition. Therefore, understanding the molecular mechanisms for the onset of metabolic disease will provide new insights for prevention and treatment. There is growing concern about the dysregulation of micro-RNAs (miRNAs) in metabolic diseases. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to untranslated regions and coding sequences of the target mRNAs. This review aims to provide recent data about the potential involvement of miRNAs in metabolic diseases, particularly obesity and type 2 diabetes.

scholarly journals RNAdetector: a free user-friendly stand-alone and cloud-based system for RNA-Seq data analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alessandro La Ferlita ◽  
Salvatore Alaimo ◽  
Sebastiano Di Bella ◽  
Emanuele Martorana ◽  
Georgios I. Laliotis ◽  
...  
Keyword(s):  
Data Analysis ◽  
Transcriptome Profiling ◽  
Biological Species ◽  
Third Party ◽  
Rna Seq ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Cross Platform ◽  
Cloud Environments ◽  
User Friendly

Abstract Background RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For this reason, dozens of pipelines have been deployed for the analysis of RNA-Seq data. Although interesting, these present several limitations and their usage require a technical background, which may be uncommon in small research laboratories. Therefore, the application of these technologies in such contexts is still limited and causes a clear bottleneck in knowledge advancement. Results Motivated by these considerations, we have developed RNAdetector, a new free cross-platform and user-friendly RNA-Seq data analysis software that can be used locally or in cloud environments through an easy-to-use Graphical User Interface allowing the analysis of coding and non-coding RNAs from RNA-Seq datasets of any sequenced biological species. Conclusions RNAdetector is a new software that fills an essential gap between the needs of biomedical and research labs to process RNA-Seq data and their common lack of technical background in performing such analysis, which usually relies on outsourcing such steps to third party bioinformatics facilities or using expensive commercial software.

scholarly journals Y-RNA and tRNA Cleavage by RNase L Mediates Terminal dsRNA Response

2016 ◽  
Author(s):  
Jesse Donovan ◽  
Sneha Rath ◽  
David Kolet-Mandrikov ◽  
Alexei Korennykh
Keyword(s):  
Small Rnas ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Rna Cleavage ◽  
Rnase L ◽  
Rna Seq ◽  
Danger Signal ◽  
Double Stranded Rna ◽  
Transfer Rnas ◽  
Non Coding Rna

AbstractDouble-stranded RNA (dsRNA) is a danger signal that triggers endonucleolytic degradation of RNA inside infected and stressed mammalian cells. This mechanism inhibits growth and ultimately removes problematic cells via apoptosis. To elucidate the molecular functions of this program and understand the connection between RNA cleavage and programmed cell death, we visualized dsRNA-induced degradation of human small RNAs using RtcB ligase-assisted RNA sequencing (RtcB RNA-seq). RtcB RNA-seq revealed strong cleavage of select transfer RNAs (tRNAs) and autoantigenic Y-RNAs, and identified the innate immune receptor RNase L as the responsible endoribonuclease. RNase L cleaves the non-coding RNA (ncRNA) targets site-specifically, releasing abundant ncRNA fragments, and downregulating full-length tRNAs and Y-RNAs. The depletion of a single Y-RNA, RNY1, appears particularly important and the loss of this Y-RNA is sufficient to initiate apoptosis. Site-specific cleavage of small ncRNA by RNase L thus emerges as an important terminal step in dsRNA surveillance.

scholarly journals Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK

2018 ◽  
Vol 96 (5) ◽  
pp. 627-635 ◽  
Author(s):  
Chunqing Wang ◽  
Hanliang He ◽  
Liang Wang ◽  
Yu Jiang ◽  
Youjia Xu
Keyword(s):  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Osteoclast Formation ◽  
Bone Homeostasis ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Altered Expression ◽  
Rna Molecules ◽  
Non Coding Rna

Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18–25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In this study, we detected the expression pattern of 10 miRNAs in serum samples from patients with osteoporosis, and identified the altered expression of 6 miRNAs by comparison with patients without osteoporosis. We selected miR-144-3p for further investigation, and showed that it regulates osteoclastogenesis by targeting RANK, and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p in CD14+ peripheral blood mononuclear cells changed TRAP activity and the osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP staining, CCK-8, and flow cytometry analyses revealed that miR-144-3p also affects osteoclast formation, proliferation, and apoptosis. Together, these results indicate that miR-144-3p critically mediates bone homeostasis, and thus, represents a promising novel therapeutic candidate for the treatment of this disease.

scholarly journals jouvence, a new human snoRNA involved in the control of cell proliferation

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Flaria El-Khoury ◽  
Jérôme Bignon ◽  
Jean-René Martin
Keyword(s):  
Cell Proliferation ◽  
Ribosome Biogenesis ◽  
Rna Seq ◽  
New Approach ◽  
Non Coding Rna ◽  
Cancerous Cell ◽  
Gut Homeostasis ◽  
Effects Of Aging ◽  
Nucleolar Rnas

Abstract Background Small nucleolar RNAs (snoRNAs) are non-coding RNAs that are conserved from archaebacteria to mammals. They are associated in the nucleolus, with proteins to form small nucleolar ribonucleoprotein (snoRNPs). They modify ribosomal RNAs, for example, the H/ACA box that converts uridine to pseudouridine. In humans, various pathologies have been associated with snoRNAs, and several snoRNAs have been reported to participate in many cancer processes. Recently, a new H/ACA box snoRNA named jouvence has been identified in Drosophila and has been shown to be involved in lifespan determination in relation to gut homeostasis. Because snoRNAs are conserved through evolution, both structurally and functionally, a jouvence orthologue has been identified in humans. RT-PCR has revealed that jouvence is expressed, suggesting that it might be functional. These results suggest the hypothesis that jouvence may display similar functions, including increasing the healthy lifespan in humans. Results Here, we report the characterization of the human snoRNA jouvence, which has not yet been annotated in the genome. We show that its overexpression significantly stimulates cell proliferation, both in various stable cancerous cell lines as well as in primary cells. By contrast, its knockdown by siRNA leads to the opposite phenotype, a rapid decrease in cell proliferation. Transcriptomic analysis (RNA-Seq) revealed that the overexpression of jouvence leads to a dedifferentiation signature of the cells. Conversely, the knockdown of jouvence led to a striking decrease in the expression levels of genes involved in ribosome biogenesis and the spliceosome. Conclusion The overexpression of a single and short non-coding RNA of 159 nucleotides, the snoRNA-jouvence, seems to be sufficient to reorient cells toward stemness, while its depletion blocks cell proliferation. In this context, we speculate that the overexpression of jouvence, which appears to be a non-canonical H/ACA snoRNA, could represent a new tool to fight against the deleterious effects of aging, while inversely, its knockdown by siRNA could represent a new approach in cancer therapy.

scholarly journals A thorough RNA-seq characterization of the porcine sperm transcriptome and its seasonal changes

2018 ◽  
Author(s):  
M. Gòdia ◽  
M. Estill ◽  
A. Castelló ◽  
S. Balasch ◽  
J.E. Rodríguez-Gil ◽  
...  
Keyword(s):  
Seasonal Changes ◽  
Cell Function ◽  
Semen Quality ◽  
Sperm Quality ◽  
Seasonal Pattern ◽  
Rna Seq ◽  
Transfer Rnas ◽  
Micro Rnas ◽  
Boar Sperm

AbstractUnderstanding the molecular basis of cell function and ultimate phenotypes is crucial for the development of biological markers. With this aim, several RNA-seq studies have been devoted to characterize the transcriptome of ejaculated spermatozoa in relation to sperm quality and fertility. Semen quality follows a seasonal pattern and decays in the summer months in several animal species. The aim of this study was to deeply profile the transcriptome of the boar sperm and to evaluate its seasonal changes. We sequenced the total and the short fractions of the sperm RNA from 10 Pietrain boars, 5 collected in summer and 5 five sampled in winter, and identified a complex and rich transcriptome with 4,436 coding genes of moderate to high abundance. Transcript fragmentation was high but less obvious in genes related to spermatogenesis, chromatin compaction and fertility. Short non-coding RNAs mostly included piwi-interacting RNAs, transfer RNAs and micro-RNAs. We also compared the transcriptome of the summer and the winter ejaculates and identified 34 coding genes and 7 micro-RNAs with a significantly distinct distribution. These genes were mostly related to oxidative stress, DNA damage and autophagy. This is the deepest characterization of the boar sperm transcriptome and the first study linking the transcriptome and the seasonal variability of semen quality in animals. The annotation described here can be used as a reference for the identification of markers of sperm quality in pigs.

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