Exploring the Potential Pathogenic Mechanisms of Asthma Deterioration Based on Modular Drivers

Asthma is a complicated chronic airway inflammatory disease caused by the interaction of genetic susceptibility and environmental impact. Although biologists have explored the pathogenesis of asthma in various aspects, the exact molecular mechanism continues to be elusive. In this study, we conducted a modular study of asthma-related genes to explore their core pathogenic driving genes. Firstly, the expression profiles of normal, mild to moderate and severe asthma patients were analyzed to screen the differentially expressed genes. Secondly, differential genes of asthma were integrated, co-expressed and clustered into modules. Next, enrichment of GO function and KEGG pathway of module genes were analyzed. Finally, non-coding RNA (ncRNA) and transcription factors that regulate modules are predicted by hypergeometric test. In summary, we have obtained 14 co-expression modules, among which CDCA5, JUNB and other genes are significantly differentially expressed in asthmatic patients, and have an active regulatory role in dysfunction module, so they are recognized as asthma-driving genes. Enrichment results showed that module genes were significantly involved in cell growth, transcription factor activity, cellular response to drugs and the transport of various ions. In addition, they also radically regulate Wnt, TGF-beta, JAK-STAT and extracellular matrix signaling pathways. Finally, we identified significant regulatory dysfunction modules of ncRNA pivot (including miR-181a-5p and let-7d-5p) and TF pivot (including NFKB1, ESR1 and MYC). Overall, our work has uncovered a co-expression network involved in the regulation of core pathogenic genes of asthma. It helps to reveal the core dysfunction modules and potential regulatory factors of this disease, and to enhance our understanding of the molecular mechanisms of asthma-related diseases.

Download Full-text

Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽

10.1530/rep-14-0095 ◽

2014 ◽

Vol 148 (1) ◽

pp. 33-41 ◽

Cited By ~ 48

Author(s):

Fulu Dong ◽

Yuan Zhang ◽

Fei Xia ◽

Yi Yang ◽

Sidong Xiong ◽

...

Keyword(s):

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Normal Pregnancy ◽

Recurrent Spontaneous Abortion ◽

Future Research ◽

Rna Molecules ◽

Non Coding Rna ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

Download Full-text

Comprehensive Analysis of Differential Expression Profiles of Long Non-coding RNAs with Associated Co-expression and Competing Endogenous RNA Networks in the Hippocampus of Patients with Alzheimer's Disease

Current Alzheimer Research ◽

10.2174/1567205018666211202143449 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jian-Jun Zhang ◽

Ze-Xuan-Zhu ◽

Guang-Min-Xu ◽

Peng Su ◽

Qian Lei ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Expression Profiles ◽

Gene Expression Omnibus ◽

Competing Endogenous Rna ◽

Pathogenic Genes ◽

Non Coding Rna ◽

Using Data ◽

Trans Regulation

Background: Alzheimer's disease (AD) is still one of the major threats to human health. Although a satisfactory treatment for AD has not yet been discovered, it is necessary to continue to search for novel approaches to deal with this insidious and debilitating disease. Although numerous studies have shown that long non-coding RNA (lncRNA) occupy a significant role in a variety of diseases, their roles in AD remain unclear. Objectives: Using data analysis to explore the role of lncRNA in the course of AD, to further our understanding of AD, and to look forward to finding a new breakthrough for the treatment of AD. Methods: We downloaded and screened expression data of the hippocampal regions of patients with AD from the Gene Expression Omnibus database. We generated lncRNA-miRNA-mRNA networks based on the competing endogenous RNA (ceRNA) hypothesis, and according to gene expression level, we constructed a coding-noncoding co-expression (CNC) network and then executed cis- and trans-regulation analyses. Results: Through comprehensive and systematic analyses, we found that lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 regulated the expression of the key AD pathogenic genes APP, PSEN1, BACE1; and that these lncRNAs may promote the distribution of β-amyloid (Aβ protein) in the brain through exosomes. In addition, lncRNAs were found to adjust viral transcriptional expression, thereby further supporting viral pathogenesis for AD. Conclusions: The lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 that are present in the hippocampus of AD patients exert an important influence on the development of this disease.

Download Full-text

Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

10.21203/rs.3.rs-618453/v1 ◽

2021 ◽

Author(s):

Nana Yang ◽

Qianghua Wang ◽

Biao Ding ◽

Yinging Gong ◽

Yue Wu ◽

...

Keyword(s):

Iron Homeostasis ◽

Molecular Mechanisms ◽

Late Onset ◽

Expression Profiles ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Ppi Network ◽

Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

Download Full-text

Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

10.21203/rs.3.rs-85830/v1 ◽

2020 ◽

Author(s):

Na Li ◽

Ru-feng Bai ◽

Chun Li ◽

Li-hong Dang ◽

Qiu-xiang Du ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Healing Process ◽

Differentially Expressed ◽

Molecular Profile ◽

Wound Age ◽

Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

Download Full-text

Comprehensive analysis of miRNA-mRNA/lncRNA during gonadal development of triploid female rainbow trout (Oncorhynchus mykiss)

10.21203/rs.3.rs-31357/v2 ◽

2020 ◽

Author(s):

Tianqing Huang ◽

Wei Gu ◽

Enhui Liu ◽

Xiulan Shi ◽

Bingqian Wang ◽

...

Keyword(s):

Rainbow Trout ◽

High Throughput Sequencing ◽

Developmental Stages ◽

Expression Profiles ◽

Noncoding Rnas ◽

Gonadal Development ◽

Differentially Expressed ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Oocyte Meiosis ◽

Non Coding Rna

Abstract Background: Chromosomal ploidy manipulation is one of the means to create excellent germplasm. Triploid fish could provide an ideal sterile model for the mechanism research of abnormality in meiosis. The complete understanding of the coding and noncoding RNAs regulating sterility caused by meiosis abnormality is still not well understood.Results: By high-throughput sequencing, we compared the expression profiles of gonadal mRNA, long non-coding RNA (lncRNA), and microRNA (miRNA) at different developmental stages [65 days post fertilisation (dpf), 180 dpf, and 600 dpf] between the diploid (XX) and triploid (XXX) female rainbow trout. A majority of differentially expressed (DE) RNAs were identified, and 22 DE mRNAs related to oocyte meiosis and homologous recombination were characterized. The predicted miRNA-mRNA/lncRNA networks of 3 developmental stages were constructed based on the target pairs of DE lncRNA-miRNA and DE mRNA-miRNA. According to the networks, meiosis-related gene of ccne1 was targeted by dre-miR-15a-5p_R+1, and 6 targeted DE lncRNAs were identified. Also, RT-qPCR was performed to validate the credibility of the network.Conclusions: This study explored the potential interplay between coding and noncoding RNAs during the gonadal development of polyploid fish. It provides full insights into polyploidy-associated effects on fertility of fish. These differentially expressed coding and noncoding RNAs provide a novel resource for studying genome diversity of polyploid induction.

Download Full-text

A Comprehensive Data Analysis of Differentially Regulated Genes in Melanoma

10.21203/rs.3.rs-19035/v1 ◽

2020 ◽

Author(s):

Yanjie Han ◽

Xinxin Li ◽

Jiliang Yan ◽

Chunyan Ma ◽

Xin Wang ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Growth Factor Receptor ◽

Principal Component ◽

Distant Metastases ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Hub Genes ◽

Ppi Networks

Abstract Background: Melanoma is the most deadly tumor in skin tumors and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma.Methods: We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553 and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples.Results: Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL) and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL and EGFR were identified in the TCGA database and melanoma tissues.Conclusions: The results suggested that FLG, DSG1, DSG3, IVL and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma.

Download Full-text

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Genes ◽

10.3390/genes11020172 ◽

2020 ◽

Vol 11 (2) ◽

pp. 172

Author(s):

Boyin Jia ◽

Yuan Liu ◽

Qining Li ◽

Jiali Zhang ◽

Chenxia Ge ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth And Development ◽

Molecular Mechanisms ◽

Muscle Development ◽

Sika Deer ◽

De Novo ◽

Expression Profiles ◽

Differentially Expressed ◽

Growth Development ◽

Development And Aging

Studies of the gene and miRNA expression profiles associated with the postnatal late growth, development, and aging of skeletal muscle are lacking in sika deer. To understand the molecular mechanisms of the growth and development of sika deer skeletal muscle, we used de novo RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) analyses to determine the differentially expressed (DE) unigenes and miRNAs from skeletal muscle tissues at 1, 3, 5, and 10 years in sika deer. A total of 51,716 unigenes, 171 known miRNAs, and 60 novel miRNAs were identified based on four mRNA and small RNA libraries. A total of 2,044 unigenes and 11 miRNAs were differentially expressed between adolescence and juvenile sika deer, 1,946 unigenes and 4 miRNAs were differentially expressed between adult and adolescent sika deer, and 2,209 unigenes and 1 miRNAs were differentially expressed between aged and adult sika deer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that DE unigenes and miRNA were mainly related to energy and substance metabolism, processes that are closely associate with the growth, development, and aging of skeletal muscle. We also constructed mRNA–mRNA and miRNA–mRNA interaction networks related to the growth, development, and aging of skeletal muscle. The results show that mRNA (Myh1, Myh2, Myh7, ACTN3, etc.) and miRNAs (miR-133a, miR-133c, miR-192, miR-151-3p, etc.) may play important roles in muscle growth and development, and mRNA (WWP1, DEK, UCP3, FUS, etc.) and miRNAs (miR-17-5p, miR-378b, miR-199a-5p, miR-7, etc.) may have key roles in muscle aging. In this study, we determined the dynamic miRNA and unigenes transcriptome in muscle tissue for the first time in sika deer. The age-dependent miRNAs and unigenes identified will offer insights into the molecular mechanism underlying muscle development, growth, and maintenance and will also provide valuable information for sika deer genetic breeding.

Download Full-text

Genome-wide analysis of differentially expressed mRNAs, lncRNAs, and circRNAs in chicken bursae of Fabricius during infection with very virulent infectious bursal disease virus

BMC Genomics ◽

10.1186/s12864-020-07129-1 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xuewei Huang ◽

Junyan Zhang ◽

Zengsu Liu ◽

Meng Wang ◽

Xiaolong Fan ◽

...

Keyword(s):

Signaling Pathway ◽

Disease Virus ◽

Infectious Bursal Disease Virus ◽

Expression Profiles ◽

Circular Rna ◽

Differentially Expressed ◽

Bursa Of Fabricius ◽

Infectious Bursal Disease ◽

Non Coding Rna ◽

Bursal Disease

Abstract Background Infectious bursal disease virus (IBDV) causes acute, highly contagious, immunosuppressive, and lethal infectious disease in young chickens and mainly infects the bursa of Fabricius (BF). To investigate interactions between IBDV and its host, RNA sequencing was applied to analyze the responses of the differentially expressed transcriptional profiles of BF infected by very virulent IBDV (vvIBDV). Results In total, 317 upregulated and 94 downregulated mRNAs were found to be significantly differentially expressed in infected chickens, compared to controls. Long non-coding RNA (lncRNA) and circular RNA (circRNA) alterations were identified in IBDV-infected chickens, and significantly different expression was observed in 272 lncRNAs and 143 circRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the functions of significantly dysregulated genes, which showed that the JAK-STAT signaling pathway, the NOD-like receptor signaling pathway, and apoptosis may be activated by IBDV infection. We predicted interactions between differentially expressed genes and produced lncRNA-mRNA and circRNA-miRNA-mRNA regulator network. Conclusions The present study identified the expression profiles of mRNAs, lncRNAs, and circRNAs during vvIBDV infection and provides new insights into the pathogenesis of IBDV and antiviral immunity of the host.

Download Full-text

PSXIII-30 Analysis of gene expression profiles in liver and muscle tissue of pigs divergent in feed efficiency

Journal of Animal Science ◽

10.1093/jas/skz258.933 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 475-475

Author(s):

Stafford Vigors ◽

Torres Sweeney

Keyword(s):

Energy Metabolism ◽

Immune Function ◽

Feed Efficiency ◽

Molecular Mechanisms ◽

Protein Targeting ◽

Expression Profiles ◽

Cell Signalling ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Joint Analysis

Abstract The improvement of feed efficiency is a key economic goal within the pig production industry. The objective of this study was to examine transcriptomic differences in both the liver and muscle in pigs divergent for feed efficiency, thus improving our understanding of the molecular mechanisms influencing feed efficiency and enabling the identification of candidate biomarkers. Residual feed intake (RFI) was calculated in two populations of pigs from two different farms of origin. The 6 most efficient (LRFI) and 6 least efficient (HRFI) animals in each population were selected for further analysis of Longissimus Dorsi muscle and liver. Three different analysis were performed: 1) Identification of differentially expressed genes (DE) in liver, 2) Identification of DE genes in muscle and 3) Identification of genes commonly DE in both tissues. Hierarchical clustering revealed that transcriptomic data segregated based on the RFI value of the pig rather than farm of origin. A total of 6464 genes were identified as being differentially expressed (DE) in muscle, while 964 genes were identified as being DE in liver. In the muscle-only analysis, genes associated with RNA, protein synthesis and energy metabolism were downregulated in the LRFI animals while in the liver-only analysis, genes associated with cell signalling and lipid homeostasis were upregulated in the LRFI animals. Genes that were commonly DE between muscle and liver (n = 526) were used for the joint analysis. These 526 genes were associated with protein targeting to membrane, extracellular matrix organization and immune function. There are pathways common to both muscle and liver in particular genes associated with immune function. In contrast, tissue-specific pathways contributing to differences in feed efficiency were also identified with genes associated with energy metabolism identified in muscle and lipid metabolism in liver. This study identifies key mechanisms driving changes in feed efficiency in pigs.

Download Full-text

Transcriptome profiling of peanut (Arachis hypogaea) gynophores in gravitropic response

Functional Plant Biology ◽

10.1071/fp13075 ◽

2013 ◽

Vol 40 (12) ◽

pp. 1249 ◽

Cited By ~ 7

Author(s):

Hai-fen Li ◽

Xiao-Ping Chen ◽

Fang-he Zhu ◽

Hai-Yan Liu ◽

Yan-Bin Hong ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Arachis Hypogaea ◽

Molecular Mechanisms ◽

Carbon Fixation ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Pentose Phosphate ◽

Differentially Expressed ◽

Pcr Analysis

Peanut (Arachis hypogaea L.) produces flowers aerially, but the fruit develops underground. This process is mediated by the gynophore, which always grows vertically downwards. The genetic basis underlying gravitropic bending of gynophores is not well understood. To identify genes related to gynophore gravitropism, gene expression profiles of gynophores cultured in vitro with tip pointing upward (gravitropic stimulation sample) and downward (control) at both 6 and 12 h were compared through a high-density peanut microarray. After gravitropic stimulation, there were 174 differentially expressed genes, including 91 upregulated and 83 downregulated genes at 6 h, and 491 differentially expressed genes including 129 upregulated and 362 downregulated genes at 12 h. The differentially expressed genes identified were assigned to 24 functional categories. Twenty pathways including carbon fixation, aminoacyl-tRNA biosynthesis, pentose phosphate pathway, starch and sucrose metabolism were identified. The quantitative real-time PCR analysis was performed for validation of microarray results. Our study paves the way to better understand the molecular mechanisms underlying the peanut gynophore gravitropism.

Download Full-text