scholarly journals Construction and analysis for dys-regulated lncRNAs and mRNAs in LPS-induced porcine PBMCs

2021 ◽  
Vol 27 (2) ◽  
pp. 170-183
Author(s):  
Jing Zhang ◽  
Xin Xu ◽  
Hongbo Chen ◽  
Ping Kang ◽  
Huiling Zhu ◽  
...  

Long non-coding RNAs (lncRNAs) are emerging as key regulators in inflammation. However, their functions and profiles in LPS-induced inflammation in pigs are largely unknown. In this study, we profiled global lncRNA and mRNA expression changes in PBMCs treated with LPS using the lncRNA-seq technique. In total 43 differentially expressed (DE) lncRNAs and 1082 DE mRNAs were identified in porcine PBMCs after LPS stimulation. Functional enrichment analysis on DE mRNAs indicated these genes were involved in inflammation-related signaling pathways, including cytokine–cytokine receptor interaction, TNF-α, NF-κB, Jak-STAT and TLR signaling pathways. In addition, co-expression network and function analysis identified the potential lncRNAs related to inflammatory response and immune response. The expressions of eight lncRNAs (ENSSSCT00000045208, ENSSSCT00000051636, ENSSSCT00000049770, ENSSSCT00000050966, ENSSSCT00000047491, ENSSSCT00000049750, ENSSSCT00000054262 and ENSSSCT00000044651) were validated in the LPS-treated PBMCs by quantitative real-time PCR (qRT-PCR). In LPS-challenged piglets, we identified that expression of three lncRNAs (ENSSSCT00000051636, ENSSSCT00000049770, and ENSSSCT00000047491) was significantly up-regulated in liver, spleen and jejunum tissues after LPS challenge, which indicated that these lncRNAs might be important regulators for inflammation. This study provides the first lncRNA and mRNA transcriptomic landscape of LPS-mediated changes in porcine PBMCs, which might provide potential insights into lncRNAs involved in regulating inflammation in pigs.

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.


Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 455 ◽  
Author(s):  
Qingyuan Ouyang ◽  
Shenqiang Hu ◽  
Guosong Wang ◽  
Jiwei Hu ◽  
Jiaman Zhang ◽  
...  

To date, research on poultry egg production performance has only been conducted within inter or intra-breed groups, while those combining both inter- and intra-breed groups are lacking. Egg production performance is known to differ markedly between Sichuan white goose (Anser cygnoides) and Landes goose (Anser anser). In order to understand the mechanism of egg production performance in geese, we undertook this study. Here, 18 ovarian stromal samples from both Sichuan white goose and Landes goose at the age of 145 days (3 individuals before egg production initiation for each breed) and 730 days (3 high- and low egg production individuals during non-laying periods for each breed) were collected to reveal the genome-wide expression profiles of ovarian mRNAs and lncRNAs between these two geese breeds at different physiological stages. Briefly, 58, 347, 797, 777, and 881 differentially expressed genes (DEGs) and 56, 24, 154, 105, and 224 differentially expressed long non-coding RNAs (DElncRNAs) were found in LLD vs. HLD (low egg production Landes goose vs. high egg production Landes goose), LSC vs. HSC (low egg production Sichuan White goose vs. high egg production Sichuan white goose), YLD vs. YSC (young Landes goose vs. young Sichuan white goose), HLD vs. HSC (high egg production Landes goose vs. high egg production Sichuan white goose), and LLD vs. LSC (low egg production Landes goose vs. low egg production Sichuan white goose) groups, respectively. Functional enrichment analysis of these DEGs and DElncRNAs suggest that the “neuroactive ligand–receptor interaction pathway” is crucial for egg production, and particularly, members of the 5-hydroxytryptamine receptor (HTR) family affect egg production by regulating ovarian metabolic function. Furthermore, the big differences in the secondary structures among HTR1F and HTR1B, HTR2B, and HTR7 may lead to their different expression patterns in goose ovaries of both inter- and intra-breed groups. These results provide novel insights into the mechanisms regulating poultry egg production performance.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5114-5114
Author(s):  
Li-Jing Shen ◽  
Fang-Yuan Chen ◽  
Lan-Fang Cao ◽  
Yong Zhang ◽  
Hua Zhong

Abstract Abstract 5114 Introduction The MYCN oncogene encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor that is frequently overexpressed in hematologic malignancies neoplasms (including acute leukemia, T-cell lymphoma, and so on). MYCN acts as a poor prognostic marker to promote an aggressive phenotype. However, the mechanisms of action and pathways affected by MYCN are still largely unclear. Methods We induced murine MYCN gene overexpression in embryonic zebrafish through heat-shock promoter and established stable germline Tg(MYCN:HSE:EGFP) zebrafish. RNA was extracted at 3 days post fertilization from wild type (WT) and transgenic zebrafish F1 generation (TG) embryo hematopoietic cells, collected by the flow cytometer, for microarray analysis. The samples were processed and subsequently analyzed in triplicate on Zebrafish Oligo Microarrays (Agilent Technologies), containing 43, 554 sets of probe, at the Advanced Throughput Inc. The microarrays were scanned in an Agilent DNA Microarray Scanner and the images were processed using Feature Extraction software. A False Discovery Rate≤0. 05 for overall interactions effect and P<0. 001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of DEG. Results Microarray analysis revealed 626 (342 genes up-regulated and 284 genes down-regulated) DEG that showed >2-fold change in TG comparing with that of WT. Using functional enrichment analysis by DAVID, several signaling pathways were regulated in TG samples (Table 1). MAPK signaling pathway was high activated through FGF, PDGF, BDNF and CACN high expression, promoting up-regulated of Ras and MKP, enhancing phosphorylation and leading to increase of cells proliferation. TGFβ signaling was inhibited by up-regulation of IFN Ã and Smad 6/7, which negative control of TGFβR and Smad 2/3. Further, we found that MYCN enhances the expression of skp2, via decreased p21 and increased CDK2, promoting cell cycle progression (Fig. 1). In addition, overexpression of MYCN weakened the function of mismatch repair, base excision repair, while increased apoptosis pathway mediated by p53 (up-regulated Bid gene). Meanwhile, Glycolysis/gluconeogenesis pathway was significantly up-regulated in TG fish. Conclusions Overexpression of MYCN induced up-regulation of cell proliferation and Glycolysis/gluconeogenesis pathway (as the Warburg effect in rapidly proliferating tumors), attenuation of repair function, all of which are phenomena associated with proliferation and malignancies transformation of blood cell feature. We found that MYCN down-regulates p27kip1, p57kip2 and p21cip1 through up-regulate Skp2, thus up-regulates CDK2, CycA, CycB, CycD and CycE. All above changes shortened the time taken to progress through the cell cycle. Increased MARK signaling and decreased TGFβ signaling pathways also contributed to promote cell cycle. (Red star marks the up-regulated genes). Disclosures: No relevant conflicts of interest to declare.


Genome ◽  
2017 ◽  
Vol 60 (12) ◽  
pp. 1021-1028 ◽  
Author(s):  
M.H. Ye ◽  
H. Bao ◽  
Y. Meng ◽  
L.L. Guan ◽  
P. Stothard ◽  
...  

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shaxi Ouyang ◽  
Yifang Liu ◽  
Changjuan Xiao ◽  
Qinghua Zeng ◽  
Xun Luo ◽  
...  

Introduction. Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. Methods. In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. Results. A total of 3 key genes—myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)—were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. Conclusions. This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ryogo Umetsu ◽  
Mizuki Tanaka ◽  
Yoko Nakayama ◽  
Yamato Kato ◽  
Natsumi Ueda ◽  
...  

Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3–22.9) and 8.2 (95% CI: 7.8–8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of “neuroactive ligand–receptor interaction.” “Mood disorders” and “major depressive disorder” were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shuqiang Li ◽  
Huijie Shao ◽  
Liansheng Chang

Epilepsy is most common in patients with tuberous sclerosis complex (TSC). However, in addition to the challenging treatment, the pathogenesis of epilepsy is still controversial. To determine the transcriptome characteristics of perituberal tissue (PT) and clarify its role in the pathogenesis of epilepsy, GSE16969 was downloaded from the GEO database for further study by comprehensive bioinformatics analysis. Identification of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein-protein interaction (PPI) network, and selection of Hub genes were performed using R language, Metascape, STRING, and Cytoscape, respectively. Comparing with cortical tuber (CT), 220 DEGs, including 95 upregulated and 125 downregulated genes, were identified in PT and mainly enriched in collagen-containing extracellular matrix and positive regulation of receptor-mediated endocytosis, as well as the pathways of ECM-receptor interaction and neuroactive ligand-receptor interaction. As for normal cortex (NC), 1549 DEGs, including 30 upregulated and 1519 downregulated genes, were identified and mainly enriched in presynapse, dendrite and axon, and also the pathways of dopaminergic synapse and oxytocin signaling pathway. In the PPI network, 4 hub modules were found between PT and CT, and top 5 hub modules were selected between PT and NC. C3, APLNR, ANXA2, CD44, CLU, CP, MCHR2, HTR1E, CTSG, APP, and GNG2 were identified as Hub genes, of which, C3, CD44, ANXA2, HTR1E, and APP were identified as Hub-BottleNeck genes. In conclusion, PT has the unique characteristics different from CT and NC in transcriptome and makes us further understand its importance in the TSC-associated epilepsy.


2021 ◽  
Vol 2021 ◽  
pp. 1-26
Author(s):  
Xiaoxi Xi ◽  
Yihong Ma ◽  
Yuzhen Xu ◽  
Anthony Chukwunonso Ogbuehi ◽  
Xiangqiong Liu ◽  
...  

Aim. To identify the critical genetic and epigenetic biomarkers by constructing the long noncoding RNA- (lncRNA-) related competing endogenous RNA (ceRNA) network involved in irreversible pulp neural inflammation (pulpitis). Materials and Methods. The public datasets regarding irreversible pulpitis were downloaded from the gene expression omnibus (GEO) database. The differential expression analysis was performed to identify the differentially expressed genes (DEGs) and DElncRNAs. Functional enrichment analysis was performed to explore the biological processes and signaling pathways enriched by DEGs. By performing a weighted gene coexpression network analysis (WGCNA), the significant gene modules in each dataset were identified. Most importantly, DElncRNA-DEmRNA regulatory network and DElncRNA-associated ceRNA network were constructed. A transcription factor- (TF-) DEmRNA network was built to identify the critical TFs involved in pulpitis. Result. Two datasets (GSE92681 and GSE77459) were selected for analysis. DEGs involved in pulpitis were significantly enriched in seven signaling pathways (i.e., NOD-like receptor (NLR), Toll-like receptor (TLR), NF-kappa B, tumor necrosis factor (TNF), cell adhesion molecules (CAMs), chemokine, and cytokine-cytokine receptor interaction pathways). The ceRNA regulatory relationships were established consisting of three genes (i.e., LCP1, EZH2, and NR4A1), five miRNAs (i.e., miR-340-5p, miR-4731-5p, miR-27a-3p, miR-34a-5p, and miR-766-5p), and three lncRNAs (i.e., XIST, MIR155HG, and LINC00630). Six transcription factors (i.e., GATA2, ETS1, FOXP3, STAT1, FOS, and JUN) were identified to play pivotal roles in pulpitis. Conclusion. This paper demonstrates the genetic and epigenetic mechanisms of irreversible pulpitis by revealing the ceRNA network. The biomarkers identified could provide research direction for the application of genetically modified stem cells in endodontic regeneration.


2021 ◽  
Vol 33 (2) ◽  
pp. 147
Author(s):  
M. Rabaglino ◽  
J. B.-M. Secher ◽  
P. Hyttel ◽  
H. Kadarmideen

In cattle, ovarian superovulation followed by invivo embryo collection and transfer (MOET), and the invitro production (IVP) of embryos are used all over the world to improve animal genetics. Application of MOET has resulted in the production of billions of healthy animals during the past 40 years, and IVP has evolved and given rise to significant numbers of calves during the past 10 years. Nevertheless, the use of MOET and IVP can affect the embryo epigenome, and therefore its transcriptome, before and after elongation, as shown by different studies. The integration of publicly available epigenome-transcriptome datasets generated by these studies could lead to a robust characterisation of the impacts of the application of MOET and IVP. The goal of this study was to integrate all publicly available data about MOET and IVP embryos to determine temporally differentially methylated regions (DMRs) and differentially expressed genes (DEGs) from blastocyst to elongation between IVP and MOET embryos. Datasets were downloaded from the Gene Expression Omnibus (GEO) database. Accession numbers were (1) for epigenomics: GSE69173, GSE97517, and GSE101895, plus one provided dataset from O’Doherty et al. (2018 BMC Genomics, 19, 438; https://doi.org/10.1186/s12864-018-4818-3), all hybridized to the EDMA platform GPL18384; (2) for transcriptomics: GSE12327, GSE21030, GSE24596, GSE24936, GSE27817, and GSE40101, all hybridized to the Affymetrix platform GPL2112. Both types of data were analysed with the limma package for R software, and functional enrichment analysis was done with the DAVID database. For DMRs, comparisons between IVP and MOET were made from spherical blastocysts (n=16 per group) on Day 7, to embryos on Day 15, specifically in the trophectoderm (TE) or embryonic disc (ED) regions (n=4 per region and per group). For DEGs, comparisons between IVP and MOET were made from spherical blastocysts (n=9 per group) to elongated blastocysts on Day 13 and embryos undergoing gastrulation on Day 16 (n=6 per group). Considering a P-value &lt;0.05 and fold-change &gt;2, there were 16 672 (TE) and 26 264 (ED) DMRs and 2236 DEGs that temporally differed between IVP and MOET. Most of the identified DMRs were found in intronic regions (around 36%) rather than exonic regions (8%). However, DMRs that were more methylated at IVP compared with MOET contained exons encoding for genes that enriched the Wnt signalling Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in the ED, and focal adhesion and ECM-receptor interaction KEGG pathways (P&lt;0.05) in the TE. Accordingly, DEGs with lower expression in elongated embryos (Day 13 and Day 16) at IVP as opposed to MOET were mainly associated with these three pathways. In conclusion, this multi-omics analysis demonstrates that even when embryos are produced under different conditions and experiments, the main changes imposed by IVP affected genes involved in embryonic development and adhesion to the endometrium, which could explain the lower survival rates at IVP compared with MOET.


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