Identification of Potential Disease Biomarkers in the Ovaries of Dolang Sheep from Xinjiang using Transcriptomics and Bioinformatics Approaches

2020 ◽  
Author(s):  
WH Chang ◽  
ZL Cui ◽  
JH Wang
Keyword(s):  
High Throughput Sequencing ◽  
Differentially Expressed ◽  
Bioinformatics Analyses ◽  
Period Gene ◽  
Disease Biomarkers ◽  
Related Information ◽  
Indigenous Breed ◽  
Health And Disease ◽  
Pathway Analyses ◽  
Molecular Regulatory Mechanisms

Background: The Dolang sheep is a well-known indigenous breed from the Xinjiang region of China. The most important characteristics of these sheep are a year-round estrus and a strong resistance to a variety of diseases. Although the molecular regulatory mechanisms governing the year-round estrus and adaptability in health and disease are well studied in various animals, the related information is limited for sheep, particularly, the Dolang variety. Methods: To identify differentially expressed genes (DEGs) that might be responsible for the year-round estrus and that are expressed under different physiological conditions in Dolang sheep, samples from ovaries collected at different reproductive periods were analyzed using high-throughput sequencing and subsequent transcriptomics and bioinformatics analyses. Result: We identified 28,717 expressed genes by RNA-Seq analysis and from a list of 987 candidate genes, we identified 308 that were differentially expressed in the ovaries of non-pregnant Dolang sheep in estrus and anestrus phases and those in the gestation phase. The genes DQA, DQB and LOC101106374 were upregulated during the gestation period. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these three genes may improve immunity and prevent the occurrence of abortion, brucellosis, toxoplasmosis and globidiosis and can be used to monitor sheep health during pregnancy. Thus, DQA, DQB and LOC101106374 may serve as potential biomarkers for monitoring disease progression as well as abortion risk during pregnancy in sheep.

scholarly journals An Integrated Analysis of Cashmere Fineness lncRNAs in Cashmere Goats

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 266 ◽  
Author(s):  
Yuan Y. Zheng ◽  
Sheng D. Sheng ◽  
Tai Y. Hui ◽  
Chang Yue ◽  
Jia M. Sun ◽  
...  
Keyword(s):  
Intermediate Filament ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Differentially Expressed ◽  
Sphingolipid Metabolism ◽  
Integrated Analysis ◽  
Messenger Rnas ◽  
Bioinformatics Analyses ◽  
Anagen Phase ◽  
Cashmere Goats

Animal growth and development are regulated by long non-coding RNAs (lncRNAs). However, the functions of lncRNAs in regulating cashmere fineness are poorly understood. To identify the key lncRNAs that are related to cashmere fineness in skin, we have collected skin samples of Liaoning cashmere goats (LCG) and Inner Mongolia cashmere goats (MCG) in the anagen phase, and have performed RNA sequencing (RNA-seq) approach on these samples. The high-throughput sequencing and bioinformatics analyses identified 437 novel lncRNAs, including 93 differentially expressed lncRNAs. We also identified 3,084 differentially expressed messenger RNAs (mRNAs) out of 27,947 mRNAs. Gene ontology (GO) analyses of lncRNAs and target genes in cis show a predominant enrichment of targets that are related to intermediate filament and intermediate filament cytoskeleton. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, sphingolipid metabolism is a significant pathway for lncRNA targets. In addition, this is the first report to reveal the possible lncRNA–mRNA regulatory network for cashmere fineness in cashmere goats. We also found that lncRNA XLOC_008679 and its target gene, KRT35, may be related to cashmere fineness in the anagen phase. The characterization and expression analyses of lncRNAs will facilitate future studies on the potential value of fiber development in LCG.

scholarly journals Regulatory network of miRNA, lncRNA, transcription factor and target immune response genes in bovine mastitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashley R. Tucker ◽  
Nicole A. Salazar ◽  
Adeola O. Ayoola ◽  
Erdoğan Memili ◽  
Bolaji N. Thomas ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Targets ◽  
Bovine Mastitis ◽  
Disease Biomarkers ◽  
Pathway Regulation ◽  
Pathway Analyses ◽  
Computational Analyses ◽  
Molecular Regulatory Mechanisms

AbstractPre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that transcription factors (TFs), lncRNAs and miRNAs modulate immune response in bovine mastitis and could potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. LncRNAs NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

scholarly journals Regulatory Network of miRNA, lncRNA, Transcription Factor and Target Immune Response Genes in Bovine Mastitis

2021 ◽  
Author(s):  
Olanrewaju Morenikeji ◽  
Ashley Tucker ◽  
Nicole Salazar ◽  
Adeola Ayoola ◽  
Erdogan Memili ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Targets ◽  
Bovine Mastitis ◽  
Disease Biomarkers ◽  
Pathway Regulation ◽  
Pathway Analyses ◽  
Computational Analyses ◽  
Molecular Regulatory Mechanisms

Abstract Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that TFs, lncRNAs and miRNAs can modulate the immune response in bovine mastitis and potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

Overexpression of miR-340-5p Inhibits Skin Fibroblast Proliferation by Targeting Kruppel-like Factor 2

2019 ◽  
Vol 20 (13) ◽  
pp. 1147-1154 ◽  
Author(s):  
Ling Chen ◽  
Qian Li ◽  
Xun Lu ◽  
Xiaohua Dong ◽  
Jingyun Li
Keyword(s):  
Gene Ontology ◽  
Skin Fibroblast ◽  
Kegg Pathway ◽  
Normal Skin ◽  
Skin Fibroblasts ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Fibroblast Proliferation ◽  
Pathway Analyses ◽  
Normal Skin Fibroblast

<P>Objective: MicroRNA (miR)-340-5p has been identified to play a key role in several cancers. However, the function of miR-340-5p in skin fibroblasts remains largely unknown. </P><P> Methods: Gain of function experiments were performed by infecting normal skin fibroblast cells with a lentivirus carrying 22-bp miR-340-5p. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. To uncover the mechanisms, mRNA-seq was used. Differentially expressed mRNAs were further determined by Gene Ontology and KEGG pathway analyses. The protein levels were analysed by Western blotting. A dual-luciferase reporter assay was used to detect the direct binding of miR-340-5p with the 3&#039;UTR of Kruppel-like factor 2 (KLF2). </P><P> Results: MiR-340-5p lentivirus infection suppressed normal skin fibroblast proliferation. The mRNAseq data revealed that 41 mRNAs were differentially expressed, including 22 upregulated and 19 downregulated transcripts in the miR-340-5p overexpression group compared with those in the control group. Gene Ontology and KEGG pathway analyses revealed that miR-340-5p overexpression correlated with the macromolecule biosynthetic process, cellular macromolecule biosynthetic process, membrane, and MAPK signalling pathway. Bioinformatics analysis and luciferase reporter assays showed that miR-340-5p binds to the 3&#039;UTR of KLF2. Forced expression of miR-340-5p decreased the expression of KLF2 in normal skin fibroblasts. Overexpression of KLF2 restored skin fibroblast proliferation in the miR-340-5p overexpression group. </P><P> Conclusion: This study demonstrates that miR-340-5p may suppress skin fibroblast proliferation, possibly through targeting KLF2. These findings could help us understand the function of miR-340-5p in skin fibroblasts. miR-340-5p could be a therapeutic target for preventing scarring.</P>

Bioinformatics Analysis and Validation of Differentially Expressed MicroRNAs with Their Target Genes Involved in GLP-1RA Facilitated Osteogenesis

2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Functional Study ◽  
Regulation Network ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Lower Expression

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.

scholarly journals Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

2021 ◽  
Author(s):  
Mayukh Banerjee ◽  
Ana Ferragut Cardoso ◽  
Laila Al-Eryani ◽  
Jianmin Pan ◽  
Theodore S. Kalbfleisch ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Mrna Expression ◽  
Hacat Cell ◽  
Arsenic Exposure ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Chronic Arsenic Exposure ◽  
Pathway Analyses ◽  
Time Point

AbstractChronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

scholarly journals Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Published Evidence

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

scholarly journals Genome-Wide Analysis of mRNA and Long Noncoding RNA Profiles in Chronic Actinic Dermatitis

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Dongyun Lei ◽  
Lechun Lv ◽  
Li Yang ◽  
Wenjuan Wu ◽  
Yong Liu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Differentially Expressed ◽  
Pathogenetic Mechanism ◽  
Bioinformatics Analyses ◽  
Inflammatory Lesions ◽  
Qrt Pcr ◽  
Exposed Skin ◽  
Genome Wide ◽  
Chronic Actinic Dermatitis ◽  
Solid Foundation

Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized by inflammatory lesions, especially on sun-exposed skin. However, its pathogenesis remains unclear. In this study, second-generation RNA sequencing and comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs) were performed to determine the transcriptome profiles of patients with CAD. A total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified. Interestingly, patients with CAD and healthy controls showed distinct transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%) lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA analyses of lncRNAs showed that inflammatory and immune response related pathways played crucial roles in the pathogenetic mechanism of CAD. In addition, we unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4 which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data validated the differentially expressed genes. The newly identified lncRNAs may have potential roles in the development of CAD; these findings lay a solid foundation for subsequent functional exploration of lncRNAs and mRNAs as therapeutic targets for CAD.

scholarly journals Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

2018 ◽  
Vol 50 (6) ◽  
pp. 2071-2085 ◽  
Author(s):  
Wentao Hu ◽  
Weiwei Pei ◽  
Lin Zhu ◽  
Jing Nie ◽  
Hailong Pei ◽  
...  
Keyword(s):  
Human Lung ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Bronchial Epithelial ◽  
Qrt Pcr ◽  
Microarray Profiling ◽  
Underlying Mechanisms ◽  
Pathway Analyses ◽  
Trans Regulation ◽  
Tgf Β1

Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.

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