scholarly journals Co-expression Network analysis of LncRNA associated with overexpression of DNMT1 in esophageal epithelial cells

2020 ◽  
Author(s):  
Yi LEI ◽  
Chen ZHANG ◽  
Dong YIN ◽  
Yi XU ◽  
Xu-feng LI ◽  
...  

Abstract Background:Screening and preliminary identification of DNMT1 high expression related LncRNA, which is involved in various inter-related signaling pathways, has revealed a theoretical basis for various types of disease mechanisms. Methods:LncRNA and mRNA differential expression profiles were identified on a microarray. The 10 LncRNAs with high levels of variation were identified by qRT-PCR. KEGG and GO analyses were used to dissect out differentially expressed mRNAs. Results and Conclusions:Six signal pathways were selected based on the KEGG results of the LncRNA-mRNAs expression network analysis.We found a total of 6987 differentially expressed LncRNAs and 7421 differentially expressed mRNAs were obtained from the microarrays in experimental and control groups (P<0.05; Fold Change >2.0x). GO analysis KEGG pathway analysis showed high expression of DNMT1 in esophageal epithelial cells. Nine pathways involved mRNA up-regulation including natural killer cell mediated cytotoxicity and many other prominent biochemical pathways. Forty six pathways were associated with down regulated mRNAs and ribosomes involving multiple biological pathways. Co-expression network analysis showed that the 8 mRNA and 16 LncRNA were linked to the P53 signaling pathway. Interactions occurred between 22 LncRNA and 11 mRNA in the ErbB signaling pathway, between 19 LncRNA and 8 mRNA in epithelial cell signal transduction of Helicobacter pylori infection. Interactions were present in 19 LncRNAs and 5 mRNAs in the sphingolipid signaling pathway along with 21 with LncRNA and 12 with mRNAs in the PI3K-Akt signaling pathway. Cytotoxicity interactions occurred with 22 LncRNAs and 9 mRNAs in natural killer cells.

2019 ◽  
Author(s):  
Dong Yin ◽  
Yi XU ◽  
Xu-feng LI ◽  
Yan CHEN

Abstract Screening and preliminary identification of DNMT1 high expression related LncRNA, which is involved in various inter-related signaling pathways, has revealed a theoretical basis for various types of disease mechanisms. LncRNA and mRNA differential expression profiles were identified on a microarray. The 10 LncRNAs with high levels of variation were identified by qRT-PCR. KEGG and GO analyses were used to dissect out differentially expressed mRNAs. Six signal pathways were selected based on the KEGG results of the LncRNA-mRNAs expression network analysis.We found a total of 6987 differentially expressed LncRNAs and 7421 differentially expressed mRNAs were obtained from the microarrays in experimental and control groups (P<0.05; Fold Change >2.0x). GO analysis KEGG pathway analysis showed high expression of DNMT1 in esophageal epithelial cells. Nine pathways involved mRNA up-regulation including natural killer cell mediated cytotoxicity and many other prominent biochemical pathways. Forty six pathways were associated with down regulated mRNAs and ribosomes involving multiple biological pathways. Co-expression network analysis showed that the 8 mRNA and 16 LncRNA were linked to the P53 signaling pathway. Interactions occurred between 22 LncRNA and 11 mRNA in the ErbB signaling pathway, between 19 LncRNA and 8 mRNA in epithelial cell signal transduction of Helicobacter pylori infection. Interactions were present in 19 LncRNAs and 5 mRNAs in the sphingolipid signaling pathway along with 21 with LncRNA and 12 with mRNAs in the PI3K-Akt signaling pathway. Cytotoxicity interactions occurred with 22 LncRNAs and 9 mRNAs in natural killer cells.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yi Lei ◽  
Yi Xu ◽  
Xu-feng Li ◽  
Yan Chen

Screening and preliminary identification of high DNMT1 expression-related lncRNA, which is involved in various interrelated signaling pathways, has led to the development of a theoretical basis for various types of disease mechanisms. Differential expression profiles of lncRNA and mRNA were identified in a microarray. Ten lncRNAs with high levels of variation were identified by qRT-PCR. KEGG and GO analyses were used to identify differentially expressed mRNAs. Six signaling pathways were selected based on the KEGG results of the lncRNA-mRNA expression network analysis. From the microarrays in the experimental and control groups, we found a total of 6987 differentially expressed lncRNAs, and 7421 differentially expressed mRNAs were obtained ( P < 0.05 ; fold   change > 2.0 x ). GO analysis and KEGG pathway analysis showed high expression of DNMT1 in esophageal epithelial cells. Nine pathways were involved in mRNA upregulation, including natural killer cell-mediated cytotoxicity and many other prominent biochemical pathways. Forty-six pathways were associated with downregulated mRNAs and ribosomes involving multiple biological pathways. Coexpression network analysis showed that 8 mRNAs and 16 lncRNAs were linked to the p53 signaling pathway. In Helicobacter pylori infections, interactions occurred between 22 lncRNAs and 11 mRNAs in the ErbB signaling pathway and between 19 lncRNAs and 8 mRNAs in epithelial cell signal transduction. Interactions were present between 19 lncRNAs and 5 mRNAs in the sphingolipid signaling pathway, along with interactions between 21 lncRNAs and 12 mRNAs in the PI3K-Akt signaling pathway. Cytotoxicity interactions occurred between 22 lncRNAs and 9 mRNAs in natural killer cells.


2020 ◽  
Author(s):  
Dawei Zhang ◽  
Wenjing Wu ◽  
Xin Huang ◽  
Ke Xu ◽  
Cheng Zheng ◽  
...  

Abstract Background: Chinese domestic pig breeds are reputed for pork quality, but their low ratio of lean-to-fat carcass weight decreases production efficiency. A better understanding of the genetic regulation network of SC fat tissue is necessary for the rational selection of Chinese domestic pig breeds. In the present study, SC adipocytes were isolated from Jiaxing Black pigs (a Chinese indigenous pig breed with redundant SC fat deposition) and Large White pigs (a lean-type pig breed with relatively low SC fat deposition) and the expression profiles of mRNAs and lncRNAs were compared by RNA-seq analysis to identify biomarkers correlated with the differences of SC fat deposition between the two breeds.Results: A total of 3,371 differentially expressed genes (DEGs) and 1,182 differentially expressed lncRNAs (DELs) were identified in SC adipocytes between Jiaxing Black (JX) and Large White (LW) pigs, which included 797 upregulated mRNAs, 2,574 downregulated mRNAs, 461 upregulated lncRNAs and 721 downregulated lncRNAs. Gene Ontology and KEGG pathway analyses revealed that the DEGs and DELs were mainly involved in the immune response, cell fate determination, PI3K-Akt signaling pathway and MAPK signaling pathway, which are known to be related to adipogenesis and lipid metabolism. The expression levels of DEGs and DELs according to the RNA-seq data were verified by quantitative PCR, which showed 81.8% consistency. The differences in MAPK pathway activity between JX and LW pigs was confirmed by western blot analysis, with <100-fold elevated p38 phosphorylation in JX pigs.Conclusions: This study offers a detailed characterization of mRNAs and lncRNAs in fat- and lean-type pig breeds. The activity of the MAPK signaling pathway was found to be associated with subcutaneous adipogenesis. These results greatly enhance our understanding of the molecular mechanisms regulating SC fat deposition in pigs.


2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  

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.


2020 ◽  
Author(s):  
Guorong Yang ◽  
Shu Tang ◽  
Jie Zhang ◽  
Ling Qin

Abstract Purpose: TRAF3IP3 is involved in the maturation of immune cells, the development of immune tissues and the immune response of the body. TRAF3IP3 is shown to expressed in a variety of malignant tumor cell lines. Down-regulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. However, the role of TRAF3IP3 in glioma is still unknown. In this study, we aimed to study the relationship between TRAF3IP3 and glioma based on TCGA data.Method: We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues. Subsequently, Kruskal-Wallis test, Wilcoxon rank sum test, and logistics regression were used to evaluate the relationship between TRAF3IP3 and clinicopathological parameters of glioma patients. GSEA was used to verify the key signal pathways involved in TRAF3IP3. We used the ssGSEA method to analyze the relationship between the expression level of TRAF3IP3 and the immune infiltration in the glioma tumor microenvironment. Finally, we used Kaplan-Meier and COX regression to evaluate the prognostic value of TRAF3IP3.Results: TRAF3IP3 transcription level was highly expressed in gliomas(P<0.001). And the high expression of TRAF3IP3 and WHO grade(OR=3.57(2.42-5.34), P<0.001), IDH status (OR=4.79(3.40-6.83), P<0.001), 1P /19q codeletion (OR=0.07(0.04-0.11), P<0.001), EGFR status (OR=2.77(1.65-4.81), P<0.001), histological type (OR=3.64(2.48-5.43), P<0.001), age (OR=1.64(1.13-2.41), P=0.01), and primary therapy outcome (OR=2.29(1.47-3.61), P<0.001) were significantly correlated. GSEA showed that six signaling pathways were significantly enriched in the TRAF3IP3 high expression phenotype group, including JAK STAT signaling pathway, interferon-γ signaling pathway, apoptosis, P53 signaling pathway, PD-1 signaling pathway, and CTLA4 signaling pathway. ssGSEA showed that the expression of TRAF3IP3 was significantly positively correlated with the infiltration of Macrophages, Th17 cells, etc. Multivariate COX regression showed that TRAF3IP3 was an independent prognostic factor for glioma OS (HR=2.169(1.301-3.615), P=0.003). Kaplan-Meier analysis showed that high expression of TRAF3IP3 was associated with worse PFS(HR=2.39(1.39-3.01), P<0.001), DFS(HR=3.02(2.27-4.01), P<0.001) and OS(HR=2.87(2.20-3.75), P<0.001).Conclusion: TRAF3IP3 may play an important role in the occurrence and development of glioma, and may be a potential biomarker for the diagnosis and prognosis of glioma.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuewei Huang ◽  
Junyan Zhang ◽  
Zengsu Liu ◽  
Meng Wang ◽  
Xiaolong Fan ◽  
...  

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.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1975 ◽  
Author(s):  
Daria Bortolotti ◽  
Valentina Gentili ◽  
Sabrina Rizzo ◽  
Antonella Rotola ◽  
Roberta Rizzo

Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells’ exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.


Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.


Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2924-2932 ◽  
Author(s):  
Xiaoqing Lu ◽  
Hovav Nechushtan ◽  
Feiying Ding ◽  
Manuel F. Rosado ◽  
Rakesh Singal ◽  
...  

AbstractDiffuse large B-cell lymphomas (DLBCLs) can be subclassified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like tumors characterized by long and short survival, respectively. In contrast to ABC-like DLBCL, GCB-like tumors exhibit high expression of components of the interleukin 4 (IL-4) signaling pathway and of IL-4 target genes such as BCL6 and HGAL, whose high expression independently predicts better survival. These observations suggest distinct activity of the IL-4 signaling pathway in DLBCL subtypes. Herein, we demonstrate similar IL-4 expression but qualitatively different IL-4 effects on GCB-like and ABC-like DLBCL. In GCB-like DLBCL, IL-4 induces expression of its target genes, activates signal transducers and activators of transcription 6 (STAT6) signaling, and increases cell proliferation. In contrast, in the ABC-like DLBCL, IL-4 activates AKT, decreases cell proliferation by cell cycle arrest, and does not induce gene expression due to aberrant Janus kinase (JAK)-STAT6 signaling attributed to STAT6 dephosphorylation. We found distinct expression profiles of tyrosine phosphatases in DLBCL subtypes and identified putative STAT6 tyrosine phosphatases—protein tyrosine phosphatase nonreceptor type 1 (PTPN1) and PTPN2, whose expression is significantly higher in ABC-like DLBCL. These differences in tyrosine phosphatase expression might underlie distinct expression profiles of some of the IL-4 target genes and could contribute to a different clinical outcome of patients with GCB-like and ABC-like DLBCLs.


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