scholarly journals RNA Sequencing Reveals Novel LncRNAs/mRNAs Network Associated with Puerarin-mediated Inhibition of Cardiac Hypertrophy in Mice

2021 ◽  
Author(s):  
Shan Ye ◽  
Wei-Yang Chen ◽  
Caiwen Ou ◽  
Min-Sheng Chen
Keyword(s):  
Mouse Model ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Biological Processes ◽  
Rna Seq ◽  
Qrt Pcr

Abstract Background: Evidence has demonstrated that puerarin is a potential drug for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs in a cardiac hypertrophy mouse model after puerarin treatment.Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to systematically analyze global gene expression. The target lncRNAs were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression (CNC) network was established to find the interaction of lncRNAs and mRNAs. The molecular functions, biological processes, molecular components and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathways analysis.Results: Puerarin exhibited obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC upregulated 19 lncRNAs and downregulated 18 lncRNAs, which could be revised by puerarin treatment (Fold change ≥ 3 and P< 0.05). Expression alterations of selected lncRNAs ENSMUST00000125726, ENSMUST00000143044 and ENSMUST00000212795 were confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was interactive relationship between those 3 validated altered lncRNAs and 5,500 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as vesicle-mediated transport, sin 3 complex, and translation initiation factor activity. KEGG analyses suggested that those lncRNA-interacted mRNAs were enriched in RNA transport, ribosome biogenesis in eukaryotes and proteasome signaling pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the ENSMUST00000125726 /ENSMUST00000143044 / ENSMUST00000212795 -mRNAs network.

scholarly journals DEBKS: A Tool to Detect Differentially Expressed Circular RNA

2020 ◽  
Author(s):  
Zelin Liu ◽  
Huiru Ding ◽  
Jianqi She ◽  
Chunhua Chen ◽  
Weiguang Zhang ◽  
...  
Keyword(s):  
Open Source ◽  
Rna Sequencing ◽  
Open Source Software ◽  
Simulated Data ◽  
Circular Rna ◽  
Host Gene ◽  
Circular Rnas ◽  
Biological Processes ◽  
Rna Seq ◽  
Disease Pathogenesis

AbstractCircular RNAs (circRNAs) are involved in various biological processes and in disease pathogenesis. However, only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species, partly because most current methods are based on circular junction counts and overlook the fact that circRNA is formed from the host gene by back-splicing (BS). To distinguish between expression originating from BS and that from the host gene, we present DEBKS, a software program to streamline the discovery of differential BS between two rRNA-depleted RNA sequencing (RNA-seq) sample groups. By applying real and simulated data and employing RT-qPCR for validation, we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups. DEBKS is available at https://github.com/yangence/DEBKS as open-source software.

scholarly journals Comprehensive genomic analysis and expression profiling of the BTB and TAZ (BT) genes in cucumber (Cucumis sativus L.)

2019 ◽  
Vol 56 (No. 1) ◽  
pp. 15-23 ◽  
Author(s):  
Yong Zhou ◽  
Guanghua Li ◽  
Lin Zhang ◽  
Jie Xu ◽  
Lifang Hu ◽  
...  
Keyword(s):  
Stress Responses ◽  
Expression Patterns ◽  
Genomic Analysis ◽  
Biological Processes ◽  
Quantitative Real Time Pcr ◽  
Cucumis Sativus L ◽  
Btb Domain ◽  
Qrt Pcr ◽  
Cucumber Genome ◽  
Bt Genes

BTB-TAZ (BT) proteins are plant-specific transcription factors containing a BTB domain and a TAZ domain. They play vital roles in various biological processes and stress responses. In this study, a total of three BT genes (CsBT1–3) were identified from cucumber genome, and they were unevenly distributed in two of the seven chromosomes. Phylogenetic analysis of the BT proteins from cucumber, Arabidopsis, apple, tomato, and rice revealed that these proteins could be distinctly divided into two groups in accordance with their motif distributions. We also determined the structures of BT genes from cucumber, Arabidopsis, and rice to demonstrate their differences. The quantitative real-time PCR (qRT-PCR) results showed that the CsBT genes displayed differential expression patterns in cucumber tissues, and their expression was regulated by cold, salt, and drought stresses. These findings suggest that CsBT genes may participate in cucumber development and responses to various abiotic stresses.

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.

scholarly journals Genome-wide characterization and expression analysis of the Dof gene family related to abiotic stress in watermelon

2019 ◽  
Author(s):  
Yong Zhou ◽  
Yuan Cheng ◽  
Chunpeng Wan ◽  
Youxin Yang ◽  
Jinyin Chen
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Family ◽  
Expression Patterns ◽  
Future Research ◽  
Biological Processes ◽  
Biological Functions ◽  
Specific Expression ◽  
Qrt Pcr ◽  
Genome Wide ◽  
Intron Structure

The plant DNA-binding with one finger (Dof) gene family is a class of plant-specific transcription factors that play vital roles in many biological processes and response to stresses. In the present study, a total of 36 ClDof genes were identified in the watermelon genome, which were unevenly distributed on 10 chromosomes. Phylogenetic analysis showed that the ClDof proteins could be divided into nine groups, and the members in a particular group had similar motif arrangement and exon-intron structure. We then analyzed the expression patterns of nine selected ClDof genes in eight specific tissues by qRT-PCR, and the results showed that they have tissue-specific expression patterns. We also evaluated the expression levels of the nine selected ClDof genes under salt stress and ABA treatments using qRT-PCR, and they showed differential expression under these treatments, suggesting their important roles in stress response. Taken together, our results provide a basis for future research on the biological functions of Dof genes in watermelon.

scholarly journals Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks

2017 ◽  
Author(s):  
John M Bryan ◽  
Temesgen D Fufa ◽  
Kapil Bharti ◽  
Brian P Brooks ◽  
Robert B Hufnagel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Mouse Retina ◽  
Human Tissues ◽  
Biological Processes ◽  
Rna Seq ◽  
Human Eye ◽  
Correlation Networks ◽  
Eye Tissues ◽  
Study Gene Expression

AbstractThe human eye is built from several specialized tissues which direct, capture, and pre-process information to provide vision. The gene expression of the different eye tissues has been extensively profiled with RNA-seq across numerous studies. Large consortium projects have also used RNA-seq to study gene expression patterning across many different human tissues, minus the eye. There has not been an integrated study of expression patterns from multiple eye tissues compared to other human body tissues. We have collated all publicly available healthy human eye RNA-seq datasets as well as dozens of other tissues. We use this fully integrated dataset to probe the biological processes and pan expression relationships between the cornea, retina, RPE-choroid complex, and the rest of the human tissues with differential expression, clustering, and GO term enrichment tools. We also leverage our large collection of retina and RPE-choroid tissues to build the first human weighted gene correlation networks and use them to highlight known biological pathways and eye gene disease enrichment. We also have integrated publicly available single cell RNA-seq data from mouse retina into our framework for validation and discovery. Finally, we make all these data, analyses, and visualizations available via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

scholarly journals Identification of lncRNAs associated with the pathogenesis of ankylosing spondylitis

2020 ◽  
Author(s):  
Dan Huang ◽  
Jian Liu ◽  
Lei Wan ◽  
Yanyan Fang ◽  
Yan Long ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Autoimmune Disease ◽  
Control Patient ◽  
Pearson Correlation ◽  
Expression Patterns ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Lncrna Expression ◽  
Qrt Pcr ◽  
And Control

Abstract Background Ankylosing spondylitis (AS) is a chronic autoimmune disease affecting the sacroiliac joint. To date, few studies have examined the association between long non-coding RNAs (lncRNAs) and AS pathogenesis. As such, we herein sought to characterize patterns of AS-related lncRNA expression and to evaluate the potential role played by these lncRNAs in this complex autoimmune context. Methods We conducted an RNA-seq analysis of peripheral blood mononuclear cell samples isolated from five AS patients and corresponding controls. These data were then leveraged to characterize AS-related lncRNA expression patterns. We further conducted GO and KEGG enrichment analyses of the parental genes encoding these lncRNAs, and we confirmed the validity of our RNA-seq data by assessing the expression of six lncRNAs via qRT-PCR in 15 AS and control patient samples. Pearson correlation analyses were additionally employed to examine the associations between the expression levels of these six lncRNAs and patient clinical index values. Results We detected 56575 total lncRNAs in AS and control patient samples during our initial RNA-seq analysis, of which 200 and 70 were found to be up- and down-regulated (FC > 2 or < 0.05; P < 0.05), respectively, in AS samples relative to controls. In qRT-PCR validation assays, we confirmed the significant upregulation of NONHSAT118801.2, ENST00000444046, and NONHSAT183847.1 and the significant downregulation of NONHSAT205110.1, NONHSAT105444.2, and NONHSAT051856.2 in AS patient samples. We further found the expression of NONHSAT118801.2 and NONHSAT183847.1 to be positively correlated with disease severity. Conclusion Overall, our findings highlight several lncRNAs that are specifically expressed in the context of AS, indicating that they may play key functions in the pathogenesis of this autoimmune disease. Specifically, we determined that NONHSAT118801.2 and NONHSAT183847.1 may be valuable biomarkers of AS.

Ribavirin, an eIF4E Inhibitor, As a Potential Anti-Lymphoma Therapeutic - Preclinical and Early Clinical Data

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3045-3045
Author(s):  
Sarah C. Rutherford ◽  
Eric Stewart ◽  
Tharu M Fernando ◽  
Biljana Culjkovic-Kraljacic ◽  
Katherine L. B. Borden ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Disease Risk ◽  
Objective Response ◽  
Antiviral Drug ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Clinical Activity ◽  
High Dose ◽  
Inadequate Response ◽  
Record System

Abstract Ribavirin, an antiviral drug used to treat infections including respiratory syncytial virus (RSV), inhibits the eukaryotic translation initiation factor 4E (eIF4E). EIF4E exports key mRNA transcripts from the nucleus and is a critical factor for translation of mRNAs into protein. Prospective trials of patients treated with ribavirin indicate that the drug has clinical activity and expected molecular effects of eIF4E inhibition in AML including relocalization of eIF4E to cytoplasm and decrease in eIF4E levels (Assouline Blood 2009 and Assouline Haematologica 2015). We demonstrated in pre-clinical models including a PDX triple hit lymphoma that eIF4E is also implicated in the pathogenesis of lymphomas (Culjkovic-Kraljacic Blood 2016). To elucidate the mechanism of action of ribavirin in DLBCL, we conducted eIF4E-immunoprecipitation followed by RNA-sequencing (RIP-seq) in OCI-Ly1 cells to identify RNAs that bind to eIF4E. We integrated this data with the RNA-sequencing of ribavirin-treated OCI-Ly1 cells (vs. vehicle) to further characterize RNAs that are more likely to be decreased by ribavirin. We performed pathway analysis with this data and found several lymphomagenic eIF4E transcripts to be significantly reduced by ribavirin treatment including the BCR, epigenomic regulators, interleukin signaling (IL-6, IL10), DNA damage response elements, and components of the splicing machinery. This suggests that ribavirin interferes with critical pathways in proliferating DLBCL cells and may be active in lymphoma patients. After observing a patient with an aggressive, refractory transformed lymphoma (CLL to HL) demonstrate an objective response on imaging following administration of ribavirin for RSV in absence of concurrent chemotherapy, we retrospectively analyzed (with IRB approval) outcomes of lymphoma patients undergoing autologous or allogeneic SCT who received ribavirin for antiviral indications. We searched our institutional electronic record system and SCT database for lymphoma patients meeting prospectively defined criteria as receiving ribavirin within 6 months prior to or any time after SCT. Ten patients were identified including 5 DLBCL (1 transformed from CLL and another from FL), 2 HL (1 transformed from CLL), 2 FL, and 1 MCL. All were male and median age at lymphoma diagnosis was 54 years (range 35-64). Median number of treatments received prior to SCT was 4 (2-8). Four were deemed to have inadequate response (3 with PD and 1 with insufficient PR) after salvage therapy and were treated with bendamustine prior to proceeding to SCT (3 with an investigational high dose regimen). Responses to therapy immediately prior to SCT included 4 CR, 5 PR, and 1 SD. Six underwent allo SCT and 4 auto SCT. All patients received ribavirin for RSV (4 inhalational, 6 oral) with a median length of treatment of 10 days (5-15). Median interval between SCT and ribavirin was 5 months (-1 to 23). Nine of 10 patients are currently alive with no evidence of lymphoma with a median OS of 17.8 months (4.6-85.5) and median PFS of 11.1 months (2.4-63.8). These retrospective data from patients with refractory lymphomas treated with ribavirin as antiviral therapy (just prior to or soon following SCT) demonstrate lymphoma-related outcomes superior to those expected based on disease risk profiles (9 of 10 with ongoing CRs). We recognize the limitations of this analysis, as well as potential selection biases and other possible explanations for these findings. However, our observations, in conjunction with preclinical data on eIF4E inhibition, raise the intriguing possibility that ribavirin may have clinically meaningful anti-lymphoma activity. Further assessment of larger numbers of patients, and rationally designed prospective clinical studies of ribavirin are justified and planned. Table Table. Disclosures Martin: Acerta: Consultancy; Novartis: Consultancy; Gilead: Consultancy, Other: travel, accommodations, expenses; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: travel, accommodations, expenses; Teva: Research Funding.

scholarly journals Exploring miRNA-mRNA regulatory network in cardiac pathology in Na+/H+ exchanger isoform 1 transgenic mice

2018 ◽  
Vol 50 (10) ◽  
pp. 846-861 ◽  
Author(s):  
Jin Xue ◽  
Dan Zhou ◽  
Orit Poulsen ◽  
Iain Hartley ◽  
Toshihiro Imamura ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Rna Sequencing ◽  
High Throughput Sequencing ◽  
Interstitial Fibrosis ◽  
Expression Patterns ◽  
Cardiac Injury ◽  
Differentially Expressed ◽  
Mrna Targets

Numerous studies have demonstrated that Na+/H+ exchanger isoform 1 (NHE1) is elevated in myocardial diseases and its effect is detrimental. To better understand the involvement of NHE1, we have previously studied cardiac-specific NHE1 transgenic mice and shown that these mice develop cardiac hypertrophy, interstitial fibrosis, and cardiac dysfunction. The purpose of current study was to identify microRNAs and their mRNA targets involved in NHE1-mediated cardiac injury. An unbiased high-throughput sequencing study was performed on both microRNAs and mRNAs. RNA sequencing showed that differentially expressed genes were enriched in hypertrophic cardiomyopathy pathway by Kyoto Encyclopedia of Genes and Genomes annotation in NHE1 transgenic hearts. These genes were classified as contraction defects (e.g., Myl2, Myh6, Mybpc3, and Actb), impaired intracellular Ca2+ homeostasis (e.g., SERCA2a, Ryr2, Rcan1, and CaMKII delta), and signaling molecules for hypertrophic cardiomyopathy (e.g., Itga/b, IGF-1, Tgfb2/3, and Prkaa1/2). microRNA sequencing revealed that 15 microRNAs were differentially expressed (2-fold, P < 0.05). Six of them (miR-1, miR-208a-3p, miR-199a-5p, miR-21-5p, miR-146a-5p, and miR-30c-5p) were reported to be related to cardiac pathological functions. The integrative analysis of microRNA and RNA sequencing data identified several crucial microRNAs including miR-30c-5p, miR-199a-5p, miR-21-5p, and miR-34a-5p as well as 10 of their mRNA targets that may affect the heart via NFAT hypertrophy and cardiac hypertrophy signaling. Furthermore, important microRNAs and mRNA targets were validated by quantitative PCR. Our study comprehensively characterizes the expression patterns of microRNAs and mRNAs, establishes functional microRNA-mRNA pairs, elucidates the potential signaling pathways, and provides novel insights on the mechanisms underlying NHE1-medicated cardiac injury.

scholarly journals Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 465-476 ◽  
Author(s):  
Jacqueline Gürke ◽  
Maria Schindler ◽  
S Mareike Pendzialek ◽  
René Thieme ◽  
Katarzyna J Grybel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Translation Initiation ◽  
Expression Patterns ◽  
Diabetic Pregnancy ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Preimplantation Embryos ◽  
Nuclear Antigen ◽  
Large Neutral Amino Acid ◽  
Dependent Manner

The mammalian target of rapamycin complex 1 (mTORC1) is known to be a central cellular nutrient sensor and master regulator of protein metabolism; therefore, it is indispensable for normal embryonic development. We showed previously in a diabetic pregnancy that embryonic mTORC1 phosphorylation is increased in case of maternal hyperglycaemia and hypoinsulinaemia. Further, the preimplantation embryo is exposed to increased L-leucine levels during a diabetic pregnancy. To understand how mTOR signalling is regulated in preimplantation embryos, we examined consequences of L-leucine and glucose stimulation on mTORC1 signalling and downstream targets inin vitrocultured preimplantation rabbit blastocysts andin vivo. High levels of L-leucine and glucose lead to higher phosphorylation of mTORC1 and its downstream target ribosomal S6 kinase 1 (S6K1) in these embryos. Further, L-leucine supplementation resulted in higher embryonic expression of genes involved in cell cycle (cyclin D1;CCND1), translation initiation (eukaryotic translation initiation factor 4E;EIF4E), amino acid transport (large neutral amino acid transporter 2; Lat2: geneSLC7A8) and proliferation (proliferating cell nuclear antigen;PCNA) in a mTORC1-dependent manner. Phosphorylation of S6K1 and expression patterns ofCCND1andEIF4Ewere increased in embryos from diabetic rabbits, while the expression of proliferation markerPCNAwas decreased. In these embryos, protein synthesis was increased and autophagic activity was decreased. We conclude that mammalian preimplantation embryos sense changes in nutrient supply via mTORC1 signalling. Therefore, mTORC1 may be a decisive mediator of metabolic programming in a diabetic pregnancy.

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