scholarly journals Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Xiao Chen ◽  
Jie Ding ◽  
Wei-Er Zhou ◽  
Xuan Zhang ◽  
Xiao-Tong Sun ◽  
...  

Dilated cardiomyopathy (DCM) is a relatively common cause of heart failure and the leading cause of heart transplantation. Aberrant changes in long non-coding RNAs (lncRNAs) are involved in DCM disorder; however, the detailed mechanisms underlying DCM initiation and progression require further investigation, and new molecular targets are needed. Here, we obtained lncRNA-expression profiles associated with DCM and non-failing hearts through microarray probe-sequence re-annotation. Weighted gene co-expression network analysis revealed a module highly associated with DCM status. Then eight hub lncRNAs in this module (FGD5-AS1, AC009113.1, WDFY3-AS2, NIFK-AS1, ZNF571-AS1, MIR100HG, AC079089.1, and EIF3J-AS1) were identified. All hub lncRNAs except ZNF571-AS1 were predicted as localizing to the cytoplasm. As a possible mechanism of DCM pathogenesis, we predicted that these hub lncRNAs might exert functions by acting as competing endogenous RNAs (ceRNAs). Furthermore, we found that the above results can be essentially reproduced in an independent external dataset. We observed the localization of hub lncRNAs by RNA-FISH in human aortic smooth muscle cells and confirmed the upregulation of the hub lncRNAs in DCM patients through quantitative RT-PCR. In conclusion, these findings identified eight candidate lncRNAs associated with DCM disease and revealed their potential involvement in DCM partly through ceRNA crosstalk. Our results facilitate the discovery of therapeutic targets and enhance the understanding of DCM pathogenesis.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Christian Besler ◽  
Daniel Urban ◽  
Stefan Watzka ◽  
Karin Klingel ◽  
Reinhard Kandolf ◽  
...  

Background: Myocarditis represents an important cause of chronic dilated cardiomyopathy. Predicting the clinical course of patients with myocarditis is difficult and the prognostic value of current histological markers remains controversial. We tested whether expression of selected microRNAs (miRNAs) in endomyocardial biopsies is related to left ventricular (LV) function and clinical events in patients with myocarditis. Methods: Endomyocardial biopsies were obtained from patients with non-inflammatory dilated cardiomyopathy (n=22) and histologically proven myocarditis (n=81). Based on literature search, we predefined a set of 6 miRNAs implicated in inflammation (miR-155, miR-146b), heart failure (miR-21, miR-133a), endothelial cell (miR-126) and skeletal muscle function (miR-206). Expression of these miRNAs in endomyocardial biopsies was quantified by RT-PCR. Results: Expression of miR-133a, miR-206 and miR-155 was markedly upregulated in endomyocardial biopsies from patients with myocarditis as compared to patients with dilated cardiomyopathy, irrespective of viral or non-viral etiology. Levels of miR-133a (R=0,68, P<0,01) and miR-155 (R=0,65, P<0,01) significantly correlated with CD68 cell count in endomyocardial biopsies from patients with myocarditis. Patients with myocarditis and preserved LV function at study entry displayed higher endomyocardial expression of miR-133a than patients with reduced LV function. Higher expression levels of miR-133a were associated with improved LV function during a mean follow-up of 3,1 years. Importantly, in a Kaplan-Meier estimate, patients with myocarditis and miR-133a levels above median showed longer survival free of death and malignant arrhythmias. Conclusion: The present study demonstrates that in a predefined set of miRNAs, relevant to cardiovascular pathology, endomyocardial miR-133a levels correlate with macrophage infiltration, improved LV function and clinical outcome in a comparatively large cohort of patients with histologically proven myocarditis. miR-133a may serve as a potential novel biomarker and therapeutic target in human myocarditis.


2021 ◽  
Vol 9 ◽  
Author(s):  
Dongxiao Cai ◽  
Bo Han ◽  
Wei Sun ◽  
Li Zhang ◽  
Jing Wang ◽  
...  

Aim: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions.Methods: The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data.Results: There were 369 up-regulated lncRNAs identified in the DCM patients (fold change &gt;2, P &lt; 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function.Conclusion: LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.


2020 ◽  
Author(s):  
Constanza Chialva ◽  
Thomas Blein ◽  
Martin Crespi ◽  
Diego Lijavetzky

ABSTRACTCarrot (Daucus carota L.) is one of the most cultivated vegetable in the world and of great importance in the human diet. Its storage organs can accumulate large quantities of anthocyanins, metabolites that confer the purple pigmentation to carrot tissues and whose biosynthesis is well characterized. Long non-coding RNAs (lncRNAs) play critical roles in regulating gene expression of various biological processes in plants. In this study, we used a high throughput stranded RNA-seq to identify and analyze the expression profiles of lncRNAs in phloem and xylem root samples using two genotypes with a strong difference in anthocyanin production. We identified 639 differentially expressed lncRNAs between genotypes, and certain were specifically associated with a particular tissue. We then established regulatory correlations between lncRNAs and anthocyanin biosynthesis genes in order to identify a molecular framework for the differential expression of the pathway between genotypes. A specific natural antisense transcript (NAT) linked to the DcMYB7 key anthocyanin biosynthetic transcription factor suggested how the regulation of this pathway may have evolved between genotypes.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Swapna Vidhur Daulatabad ◽  
Rajneesh Srivastava ◽  
Sarath Chandra Janga

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.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huili Qiao ◽  
Jingya Wang ◽  
Yuanzhuo Wang ◽  
Juanjuan Yang ◽  
Bofan Wei ◽  
...  

Abstract Background 20-hydroxyecdysone (20E) plays important roles in insect molting and metamorphosis. 20E-induced autophagy has been detected during the larval–pupal transition in different insects. In Bombyx mori, autophagy is induced by 20E in the larval fat body. Long non-coding RNAs (lncRNAs) function in various biological processes in many organisms, including insects. Many lncRNAs have been reported to be potential for autophagy occurrence in mammals, but it has not been investigated in insects. Results RNA libraries from the fat body of B. mori dissected at 2 and 6 h post-injection with 20E were constructed and sequenced, and comprehensive analysis of lncRNAs and mRNAs was performed. A total of 1035 lncRNAs were identified, including 905 lincRNAs and 130 antisense lncRNAs. Compared with mRNAs, lncRNAs had longer transcript length and fewer exons. 132 lncRNAs were found differentially expressed at 2 h post injection, compared with 64 lncRNAs at 6 h post injection. Thirty differentially expressed lncRNAs were common at 2 and 6 h post-injection, and were hypothesized to be associated with the 20E response. Target gene analysis predicted 6493 lncRNA-mRNA cis pairs and 42,797 lncRNA-mRNA trans pairs. The expression profiles of LNC_000560 were highly consistent with its potential target genes, Atg4B, and RNAi of LNC_000560 significantly decreased the expression of LNC_000560 and Atg4B. These results indicated that LNC_000560 was potentially involved in the 20E-induced autophagy of the fat body by regulating Atg4B. Conclusions This study provides the genome-wide identification and functional characterization of lncRNAs associated with 20E-induced autophagy in the fat body of B. mori. LNC_000560 and its potential target gene were identified to be related to 20-regulated autophagy in B. mori. These results will be helpful for further studying the regulatory mechanisms of lncRNAs in autophagy and other biological processes in this insect model.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1839
Author(s):  
Karolina Seborova ◽  
Radka Vaclavikova ◽  
Lukas Rob ◽  
Pavel Soucek ◽  
Pavel Vodicka

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk

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.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2006
Author(s):  
Hongyu Liu ◽  
Ibrar Muhammad Khan ◽  
Huiqun Yin ◽  
Xinqi Zhou ◽  
Muhammad Rizwan ◽  
...  

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.


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