Long non-coding RNAs (lncRNAs) in skeletal and cardiac muscle: potential therapeutic and diagnostic targets?

2016 ◽  
Vol 130 (24) ◽  
pp. 2245-2256 ◽  
Author(s):  
Julie R. McMullen ◽  
Brian G. Drew
Keyword(s):  
Cardiac Muscle ◽  
Striated Muscle ◽  
Cell Types ◽  
Diagnostic Tools ◽  
Transcriptional Networks ◽  
Sequencing Technology ◽  
Enormous Amount ◽  
Non Coding Rnas ◽  
Novel Therapeutic ◽  
Muscle Potential

The recent discovery that thousands of RNAs are transcribed by the cell but are never translated into protein, highlights a significant void in our current understanding of how transcriptional networks regulate cellular function. This is particularly astounding when we consider that over 75% of the human genome is transcribed into RNA, but only approximately 2% of RNA is translated into known proteins. This raises the question as to what function the other so-called ‘non-coding RNAs’ (ncRNAs) are performing in the cell. Over the last decade, an enormous amount of research has identified several classes of ncRNAs, predominantly short ncRNAs (<200 nt) that have been confirmed to have functional significance. Recent advances in sequencing technology and bioinformatics have also allowed for the identification of a novel class of ncRNAs, termed long ncRNA (lncRNA) (>200 nt). Several studies have recently shown that long non-coding RNAs (lncRNAs) are associated with tissue development and disease, particularly in cell types that undergo differentiation such as stem cells, cancer cells and striated muscle (skeletal/cardiac). Therefore, understanding the function of these lncRNAs and designing strategies to detect and manipulate them, may present novel therapeutic and diagnostic opportunities. This review will explore the current literature on lncRNAs in skeletal and cardiac muscle and discuss their recent implication in development and disease. Lastly, we will also explore the possibility of using lncRNAs as therapeutic and diagnostic tools and discuss the opportunities and potential shortcomings to these applications.

scholarly journals miRquant 2.0: an Expanded Tool for Accurate Annotation and Quantification of MicroRNAs and their isomiRs from Small RNA-Sequencing Data

2016 ◽  
Vol 13 (5) ◽  
Author(s):  
Matthew Kanke ◽  
Jeanette Baran-Gale ◽  
Jonathan Villanueva ◽  
Praveen Sethupathy
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
Cell Types ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Sequencing Technology ◽  
Additional Information ◽  
Disease States ◽  
Non Coding Rnas ◽  
The Rich

SummarySmall non-coding RNAs, in particular microRNAs, are critical for normal physiology and are candidate biomarkers, regulators, and therapeutic targets for a wide variety of diseases. There is an ever-growing interest in the comprehensive and accurate annotation of microRNAs across diverse cell types, conditions, species, and disease states. Highthroughput sequencing technology has emerged as the method of choice for profiling microRNAs. Specialized bioinformatic strategies are required to mine as much meaningful information as possible from the sequencing data to provide a comprehensive view of the microRNA landscape. Here we present miRquant 2.0, an expanded bioinformatics tool for accurate annotation and quantification of microRNAs and their isoforms (termed isomiRs) from small RNA-sequencing data. We anticipate that miRquant 2.0 will be useful for researchers interested not only in quantifying known microRNAs but also mining the rich well of additional information embedded in small RNA-sequencing data.

Adipocytes-released Peptides Involved in the Control of Gastrointestinal Motility

2019 ◽  
Vol 20 (6) ◽  
pp. 614-629 ◽  
Author(s):  
Eglantina Idrizaj ◽  
Rachele Garella ◽  
Roberta Squecco ◽  
Maria Caterina Baccari
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Gastrointestinal Motility ◽  
Diagnostic Tools ◽  
Therapeutic Approaches ◽  
Motor Responses ◽  
Gastrointestinal Motor ◽  
Treatment Of Obesity ◽  
Novel Therapeutic

The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.

scholarly journals Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins

2021 ◽  
Vol 22 (8) ◽  
pp. 4256
Author(s):  
Lorenzo Maggi ◽  
Manolis Mavroidis ◽  
Stelios Psarras ◽  
Yassemi Capetanaki ◽  
Giovanna Lattanzi
Keyword(s):  
Muscular Dystrophy ◽  
Cardiac Muscle ◽  
Intermediate Filament ◽  
Striated Muscle ◽  
Congenital Muscular Dystrophy ◽  
Left Ventricular ◽  
Intermediate Filament Proteins ◽  
Muscle Disorders ◽  
Genes Encoding ◽  
Molecular Aspects

Intermediate filaments are major components of the cytoskeleton. Desmin and synemin, cytoplasmic intermediate filament proteins and A-type lamins, nuclear intermediate filament proteins, play key roles in skeletal and cardiac muscle. Desmin, encoded by the DES gene (OMIM *125660) and A-type lamins by the LMNA gene (OMIM *150330), have been involved in striated muscle disorders. Diseases include desmin-related myopathy and cardiomyopathy (desminopathy), which can be manifested with dilated, restrictive, hypertrophic, arrhythmogenic, or even left ventricular non-compaction cardiomyopathy, Emery–Dreifuss Muscular Dystrophy (EDMD2 and EDMD3, due to LMNA mutations), LMNA-related congenital Muscular Dystrophy (L-CMD) and LMNA-linked dilated cardiomyopathy with conduction system defects (CMD1A). Recently, mutations in synemin (SYNM gene, OMIM *606087) have been linked to cardiomyopathy. This review will summarize clinical and molecular aspects of desmin-, lamin- and synemin-related striated muscle disorders with focus on LMNA and DES-associated clinical entities and will suggest pathogenetic hypotheses based on the interplay of desmin and lamin A/C. In healthy muscle, such interplay is responsible for the involvement of this network in mechanosignaling, nuclear positioning and mitochondrial homeostasis, while in disease it is disturbed, leading to myocyte death and activation of inflammation and the associated secretome alterations.

scholarly journals Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Non Coding Rnas ◽  
Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

scholarly journals Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

2021 ◽  
Vol 22 (4) ◽  
pp. 1539
Author(s):  
Paola De Sanctis ◽  
Giuseppe Filardo ◽  
Provvidenza Maria Abruzzo ◽  
Annalisa Astolfi ◽  
Alessandra Bolotta ◽  
...  
Keyword(s):  
Exercise Training ◽  
High Intensity ◽  
Vastus Lateralis ◽  
Mammalian Target Of Rapamycin ◽  
Differentially Expressed ◽  
Transcriptional Networks ◽  
Vastus Lateralis Muscle ◽  
Age Related ◽  
Wide Range ◽  
Non Coding Rnas

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

scholarly journals Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

2020 ◽  
Vol 22 (1) ◽  
pp. 261
Author(s):  
Abdelnaby Khalyfa ◽  
Wesley Warren ◽  
Jorge Andrade ◽  
Christopher A. Bottoms ◽  
Edward S. Rice ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cell Types ◽  
Cellular Level ◽  
Cellular Heterogeneity ◽  
Transcriptional Networks ◽  
Metabolic Dysfunction ◽  
Rna Seq ◽  
Obstructive Sleep ◽  
Differential Expressed Gene ◽  
Key Aspects

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.

Applying Probe Electrospray Ionization Mass Spectrometry to Cytological Diagnosis: A Preliminary Study by Using Cultured Lung Cancer Cells

2021 ◽  
pp. 1-10
Author(s):  
Yuki Morimoto ◽  
Takeshi Oya ◽  
Mayuko Ichimura-Shimizu ◽  
Minoru Matsumoto ◽  
Hirohisa Ogawa ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Squamous Cell ◽  
Cultured Cells ◽  
Sample Pretreatment ◽  
Cell Types ◽  
Diagnostic Tools ◽  
Ionization Mass ◽  
Diagnostic Modality ◽  
Probe Electrospray Ionization

<b><i>Objectives:</i></b> Cytology and histology are 2 indispensable diagnostic tools for cancer diagnosis, which are rapidly increasing in importance with aging populations. We applied mass spectrometry (MS) as a rapid approach for swiftly acquiring nonmorphological information of interested cells. Conventional MS, which primarily rely on promoting ionization by pre-applying a matrix to cells, has the drawback of time-consuming both on data acquisition and analysis. As an emerging method, probe electrospray ionization-MS (PESI-MS) with a dedicated probe is capable to pierce sample and measure specimen in small amounts, either liquid or solid, without the requirement for sample pretreatment. Furthermore, PESI-MS is timesaving compared to the conventional MS. Herein, we investigated the capability of PESI-MS to characterize the cell types derived from the respiratory tract of human tissues. <b><i>Study Design:</i></b> PESI-MS analyses with DPiMS-2020 were performed on various type of cultured cells including 5 lung squamous cell carcinomas, 5 lung adenocarcinomas, 5 small-cell carcinomas, 4 malignant mesotheliomas, and 2 normal controls. <b><i>Results:</i></b> Several characteristic peaks were detected at around m/z 200 and 800 that were common in all samples. As expected, partial least squares-discriminant analysis of PESI-MS data distinguished the cancer cell types from normal control cells. Moreover, distinct clusters divided squamous cell carcinoma from adenocarcinoma. <b><i>Conclusion:</i></b> PESI-MS presented a promising potential as a novel diagnostic modality for swiftly acquiring specific cytological information.

Histological observations on precystic merogony and metrocyte formation of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in varying lemmings, Dicrostonyx richardsoni

1985 ◽  
Vol 63 (12) ◽  
pp. 2907-2912 ◽  
Author(s):  
Richard J. Cawthorn ◽  
Ronald J. Brooks
Keyword(s):  
Cardiac Muscle ◽  
Dose Response ◽  
Striated Muscle ◽  
Cyst Formation ◽  
Endogenous Development

This study was designed to elucidate the early endogenous development of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in varying lemmings, Dicrostonyx richardsoni. After determining the dose–response effects of sporocysts of S. rauschorum on lemmings (doses greater than 500 sporocysts were lethal during hepatic merogony), sporocysts were administered to additional lemmings that were killed beginning 1 day postinoculation (DPI) and continuing to 15.0 DPI. Merogony of S. rauschorum occurs in hepatocytes 4 – 6 DPI; merozoites were also found in leucocytes 5 – 6 DPI in liver impression smears. Cyst formation began 9.0 DPI in striated muscle (rarely in cardiac muscle) and only metrocytes were present to 15.0 DPI. Overall, S. rauschorum has only one precystic generation of merogony, in hepatocytes, and then rapidly forms cysts containing metrocytes in striated musculature.

scholarly journals Adhesive multiplicity in the interaction of embryonic fibroblasts and myoblasts with extracellular matrices.

1984 ◽  
Vol 99 (4) ◽  
pp. 1398-1404 ◽  
Author(s):  
C Decker ◽  
R Greggs ◽  
K Duggan ◽  
J Stubbs ◽  
A Horwitz
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Extracellular Matrices ◽  
Common Denominator ◽  
Cell Matrix ◽  
Skeletal Myoblasts ◽  
A Cell ◽  
Cell Matrix Adhesion

Neff et al. (1982, J. Cell Biol., 95:654-666) have described a monoclonal antibody, CSAT, directed against a cell surface antigen that participates in the adhesion of skeletal muscle to extracellular matrices. We used the same antibody to compare and parse the determinants of adhesion and morphology on myogenic and fibrogenic cells. We report here that the antigen is present on skeletal and cardiac muscle and on tendon, skeletal, dermal, and cardiac fibroblasts; however, its contribution to their morphology and adhesion is different. The antibody produces large alterations in the morphology and adhesion of skeletal myoblasts and tendon fibroblasts; in contrast, its effects on the cardiac fibroblasts are not readily detected. The effects of CSAT on the other cell types, i.e., dermal and skeletal fibroblasts, cardiac muscle, 5-bromodeoxyuridine-treated skeletal muscle, lie between these extremes. The effects of CSAT on the skeletal myoblasts depends on the calcium concentration in the growth medium and on the culture age. We interpret these differential responses to CSAT as revealing differences in the adhesion of the various cells to extracellular matrices. This interpretation is supported by parallel studies using quantitative assays of cell-matrix adhesion. The likely origin of these adhesive differences is the progressive display of different kinds of adhesion-related molecules and their organizational complexes on increasingly adhesive cells. The antigen to which CSAT is directed is present on all of the above cells and thus appears to be a lowest common denominator of their adhesion to extracellular matrices.

scholarly journals Mechanisms in allergic airway inflammation – lessons from studies in the mouse

2008 ◽  
Vol 10 ◽  
Author(s):  
Bennett O.V. Shum ◽  
Michael S. Rolph ◽  
William A. Sewell
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Cellular Response ◽  
Allergic Airway Inflammation ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Chronic Inflammatory Disease ◽  
Pathological Feature ◽  
Cytokines And Chemokines ◽  
Novel Therapeutic

Asthma is a chronic inflammatory disease of the airways, involving recurrent episodes of airway obstruction and wheezing. A common pathological feature in asthma is the presence of a characteristic allergic airway inflammatory response involving extensive leukocyte infiltration, mucus overproduction and airway hyper-reactivity. The pathogenesis of allergic airway inflammation is complex, involving multiple cell types such as T helper 2 cells, regulatory T cells, eosinophils, dendritic cells, mast cells, and parenchymal cells of the lung. The cellular response in allergic airway inflammation is controlled by a broad range of bioactive mediators, including IgE, cytokines and chemokines. The asthmatic allergic inflammatory response has been a particular focus of efforts to develop novel therapeutic agents. Animal models are widely used to investigate inflammatory mechanisms. Although these models are not perfect replicas of clinical asthma, such studies have led to the development of numerous novel therapeutic agents, of which some have already been successful in clinical trials.

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