A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders.
Ontology highlight
ABSTRACT:
SUBMITTER: Ghanbari M
PROVIDER: S-EPMC6894420 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders.
Ghanbari Mohsen M Peters Marjolein J MJ de Vries Paul S PS Boer Cindy G CG van Rooij Jeroen G J JGJ Lee Yu-Chi YC Kumar Vinod V Uitterlinden André G AG Ikram M Arfan MA Wijmenga Cisca C Ordovas Jose M JM Smith Caren E CE van Meurs Joyce B J JBJ Erkeland Stefan J SJ Franco Oscar H OH Dehghan Abbas A
Journal of human genetics 20180130 4
Genome-wide association studies (GWAS) have identified many susceptibility loci for cardiometabolic disorders. Most of the associated variants reside in non-coding regions of the genome including long non-coding RNAs (lncRNAs), which are thought to play critical roles in diverse biological processes. Here, we leveraged data from the available GWAS meta-analyses on lipid and obesity-related traits, blood pressure, type 2 diabetes, and coronary artery disease and identified 179 associated single-n ...[more]
Similar Datasets
Project description:Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic regulation, development, and disease. Despite growing interest in lncRNAs, the mechanisms by which lncRNAs control cellular processes are still elusive. Improved understanding of these mechanisms is critical, because the majority of the mammalian genome is transcribed, in most cases resulting in non-coding RNA products. Recent studies have suggested the involvement of lncRNA in neurobehavioral and neurodevelopmental disorders, highlighting the functional importance of this subclass of brain-enriched RNAs. Impaired expression of lnRNAs has been implicated in several forms of intellectual disability disorders. However, the role of this family of RNAs in cognitive function is largely unknown. Here we provide an overview of recently identified mechanisms of neuronal development involving lncRNAs, and the consequences of lncRNA deregulation for neurodevelopmental disorders.
| S-EPMC3874560 | biostudies-literature
Project description:Among thousands of long non-coding RNAs (lncRNAs) only a small subset is functionally characterized and the functional annotation of lncRNAs on the genomic scale remains inadequate. In this study we computationally characterized two functionally different parts of human lncRNAs transcriptome based on their ability to bind the polycomb repressive complex, PRC2. This classification is enabled by the fact that while all lncRNAs constitute a diverse set of sequences, the classes of PRC2-binding and PRC2 non-binding lncRNAs possess characteristic combinations of sequence-structure patterns and, therefore, can be separated within the feature space. Based on the specific combination of features, we built several machine-learning classifiers and identified the SVM-based classifier as the best performing. We further showed that the SVM-based classifier is able to generalize on the independent data sets. We observed that this classifier, trained on the human lncRNAs, can predict up to 59.4% of PRC2-binding lncRNAs in mice. This suggests that, despite the low degree of sequence conservation, many lncRNAs play functionally conserved biological roles.
| S-EPMC3441527 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is a prevalent aggressive malignant tumor with poor prognosis. Investigations into the molecular changes that occur as a result of the disease, as well as identification of novel biomarkers for its diagnosis and prognosis, are urgently required. Long non?coding RNAs (lncRNAs) have been reported to play a critical role in tumor progression. The present study performed data mining analyses for ESCC via an integrated study of accumulated datasets and identification of the differentially expressed lncRNAs from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The identified intersection of differentially expressed genes (lncRNAs, miRNAs and mRNAs) in ESCC tissues between the GEO and TCGA datasets was investigated. Based on these intersected lncRNAs, the present study constructed a competitive endogenous RNA (ceRNA) network of lncRNAs in ESCC. A total of 81 intersection lncRNAs were identified; 67 of these were included in the ceRNA network. Functional analyses revealed that these 67 key lncRNAs primarily dominated cellular biological processes. The present study then analyzed the associations between the expression levels of these 67 key lncRNAs and the clinicopathological characteristics of the ESCC patients, as well as their survival time using TCGA. The results revealed that 31 of these lncRNAs were associated with tumor grade, tumor?node?metastasis (TNM) stage and lymphatic metastasis status (P<0.05). In addition, 15 key lncRNAs were demonstrated to be associated with survival time (P<0.05). Finally, 5 key lncRNAs were selected for validation of their expression levels in 30 patients newly diagnosed with ESCC via reverse transcription?quantitative PCR (RT?qPCR). The results suggested that the fold changes in the trends of up? and downregulation between GEO, TCGA and RT?qPCR were consistent. In addition, it was also demonstrated that a select few of these 5 key lncRNAs were significantly associated with TNM stage and lymph node metastasis (P<0.05). The results of the clinically relevant analysis and the aforementioned bioinformatics were similar, hence proving that the bioinformatics analysis used in the present study is credible. Overall, the results from the present study may provide further insight into the functional characteristics of lncRNAs in ESCC through bioinformatics integrative analysis of the GEO and TCGA datasets, and reveal potential diagnostic and prognostic biomarkers for ESCC.
| S-EPMC6859451 | biostudies-literature
Project description:The potential function of long non-coding RNAs in regulating neighbor protein-coding genes has attracted scientists' attention. Despite the important role of lncRNAs in biological processes, a limited number of studies focus on non-model animal lncRNAs. In this study, we used a stringent step-by-step filtering pipeline and machine learning-based tools to identify the specific Androctonus crassicauda lncRNAs and analyze the features of predicted scorpion lncRNAs. 13,401 lncRNAs were detected using pipeline in A. crassicauda transcriptome. The blast results indicated that the majority of these lncRNAs sequences (12,642) have no identifiable orthologs even in closely related species and those considered as novel lncRNAs. Compared to lncRNA prediction tools indicated that our pipeline is a helpful approach to distinguish protein-coding and non-coding transcripts from RNA sequencing data of species without reference genomes. Moreover, analyzing lncRNA characteristics in A. crassicauda uncovered that lower protein-coding potential, lower GC content, shorter transcript length, and less number of isoform per gene are outstanding features of A. crassicauda lncRNAs transcripts.
| S-EPMC7907363 | biostudies-literature
Project description:Genetic and environmental factors, alone or in combination, contribute to the pathogenesis of autism spectrum disorder (ASD). Although many protein-coding genes have now been identified as disease risk genes for ASD, a detailed illustration of long non-coding RNAs (lncRNAs) associated with ASD remains elusive. In this study, we first identified ASD-related lncRNAs based on genomic variant data of individuals with ASD from a twin study. In total, 532 ASD-related lncRNAs were identified, and 86.7% of these ASD-related lncRNAs were further validated by an independent copy number variant (CNV) dataset. Then, the functions and associated biological pathways of ASD-related lncRNAs were explored by enrichment analysis of their three different types of functional neighbor genes (i.e., genomic neighbors, competing endogenous RNA (ceRNA) neighbors, and gene co-expression neighbors in the cortex). The results have shown that most of the functional neighbor genes of ASD-related lncRNAs were enriched in nervous system development, inflammatory responses, and transcriptional regulation. Moreover, we explored the differential functions of ASD-related lncRNAs in distinct brain regions by using gene co-expression network analysis based on tissue-specific gene expression profiles. As a set, ASD-related lncRNAs were mainly associated with nervous system development and dopaminergic synapse in the cortex, but associated with transcriptional regulation in the cerebellum. In addition, a functional network analysis was conducted for the highly reliable functional neighbor genes of ASD-related lncRNAs. We found that all the highly reliable functional neighbor genes were connected in a single functional network, which provided additional clues for the action mechanisms of ASD-related lncRNAs. Finally, we predicted several potential drugs based on the enrichment of drug-induced pathway sets in the ASD-altered biological pathway list. Among these drugs, several (e.g., amoxapine, piperine, and diflunisal) were partly supported by the previous reports. In conclusion, ASD-related lncRNAs participated in the pathogenesis of ASD through various known biological pathways, which may be differential in distinct brain regions. Detailed investigation into ASD-related lncRNAs can provide clues for developing potential ASD diagnosis biomarkers and therapy.
| S-EPMC7525012 | biostudies-literature
Project description:In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging. The Developmental Genome Anatomy Project (DGAP) and similar projects recruit individuals with apparently balanced chromosomal abnormalities (BCAs) that disrupt or dysregulate genes in order to annotate the human genome. We hypothesized that rearrangements disrupting lncRNAs could be the underlying genetic etiology for the phenotypes of a subset of these individuals. Thus, we assessed 279 cases with BCAs and selected 191 cases with simple BCAs (breakpoints at only two genomic locations) for further analysis of lncRNA disruptions. From these, we identified 66 cases in which the chromosomal rearrangements directly disrupt lncRNAs. Strikingly, the lncRNAs MEF2C-AS1 and ENSG00000257522 are each disrupted in two unrelated cases. Furthermore, in 30 cases, no genes of any other class aside from lncRNAs are directly disrupted, consistent with the hypothesis that lncRNA disruptions could underly the phenotypes of these individuals. To showcase the power of this genomic approach for annotating lncRNAs, here we focus on clinical reports and genetic analysis of two individuals with BCAs and additionally highlight six individuals with likely developmental etiologies due to lncRNA disruptions.
| S-EPMC11213069 | biostudies-literature
Project description:Single-gene defects have been revealed to be the etiologies of many kidney diseases with the recent advances in molecular genetics. Autosomal dominant polycystic kidney disease (ADPKD), as one of the most common inherited kidney diseases, is caused by mutations of PKD1 or PKD2 gene. Due to the complexity of pathophysiology of cyst formation and progression, limited therapeutic options are available. The roles of noncoding RNAs in development and disease have gained widespread attention in recent years. In particular, microRNAs in promoting PKD progression have been highlighted. The dysregulated microRNAs modulate cyst growth through suppressing the expression of PKD genes and regulating cystic renal epithelial cell proliferation, mitochondrial metabolism, apoptosis and autophagy. The antagonists of microRNAs have emerged as potential therapeutic drugs for the treatment of ADPKD. In addition, studies have also focused on microRNAs as potential biomarkers for ADPKD and other common hereditary kidney diseases, including HNF1β-associated kidney disease, Alport syndrome, congenital abnormalities of the kidney and urinary tract (CAKUT), von Hippel-Lindau (VHL) disease, and Fabry disease. This review assembles the current understanding of the non-coding RNAs, including microRNAs and long noncoding RNAs, in polycystic kidney disease and these common monogenic kidney diseases.
| S-EPMC7998154 | biostudies-literature
Project description:Multiple myeloma (MM) is a clonal proliferation of bone marrow plasma cells characterized by highly heterogeneous genetic background and clinical course, whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis and tumor evolution. Although still in its infancy, the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts. In the present study investigating a cohort of 30 MM patients, a deep RNA-sequencing analysis overwhelmed previous array studies and allowed the most accurate definition of lncRNA transcripts structure and expression, ultimately providing a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. Despite the small number of analyzed samples, the high accuracy of RNA-sequencing approach for complex transcriptome processing led to the identification of 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship.
| S-EPMC5920050 | biostudies-literature
Project description:BACKGROUND: Recent analysis of the mouse transcriptional data has revealed the existence of approximately 34,000 messenger-like non-coding RNAs (ml-ncRNAs). Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. RESULTS: A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir) for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel) strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 x 10(-16)) with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800) in the ml-ncRNAs population. CONCLUSION: Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.
| S-EPMC2410135 | biostudies-literature
Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
| S-EPMC9654895 | biostudies-literature