scholarly journals Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruining Liu ◽  
Gang Li ◽  
Haoli Ma ◽  
Xianlong Zhou ◽  
Pengcheng Wang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Signaling Pathway ◽  
Wistar Rats ◽  
Cholesterol Metabolism ◽  
Expression Profiles ◽  
Receptor Interaction ◽  
Pathophysiological Mechanism ◽  
Rna Seq ◽  
Diaphragmatic Dysfunction ◽  
Controlled Mechanical Ventilation

Abstract Background Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. Results The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. Conclusions This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD.

scholarly journals A Novel lnc-RNA, Named lnc-ORA, Is Identified by RNA-Seq Analysis, and Its Knockdown Inhibits Adipogenesis by Regulating the PI3K/AKT/mTOR Signaling Pathway

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 477 ◽  
Author(s):  
Rui Cai ◽  
Guorong Tang ◽  
Que Zhang ◽  
Wenlong Yong ◽  
Wanrong Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mtor Signaling ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Mtor Signaling Pathway ◽  
Mrna And Protein Expression

Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine–cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.

scholarly journals Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White Pigs

2020 ◽  
Author(s):  
Dawei Zhang ◽  
Wenjing Wu ◽  
Xin Huang ◽  
Ke Xu ◽  
Cheng Zheng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Fat Deposition ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Domestic Pig ◽  
Large White ◽  
Pig Breeds

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.

Expression profile analysis of Differentially Expressed Genes in Human Coronary Artery Endothelial Cells Induced by Serum from Kawasaki Disease: A preliminary study

2020 ◽  
Author(s):  
Xue Fan ◽  
Meng Li ◽  
Min Xiao ◽  
Cong Liu ◽  
Mingguo Xu
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Kawasaki Disease ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Healthy Children ◽  
Rna Seq ◽  
Human Coronary Artery

Abstract Background: Kawasaki disease (KD) leads to coronary artery damage and the etiology of KD is unknown. The present study was designed to explore the differentially expressed genes (DEGs) in KD serum-induced human coronary artery endothelial cells (HCAECs) by RNA-sequence (RNA-seq). Methods: HCAECs were stimulated with serum (15% (v/v)), which were collected from 20 healthy children and 20 KD patients, for 24 hours. DEGs were then detected and analyzed by RNA-seq and bioinformatics analysis. Results: The expression of SMAD1, SMAD6, CD34, CXCL1, PITX2, and APLN was validated by qPCR. 102 genes, 59 up-regulated and 43 down-regulated genes, were significantly differentially expressed in KD groups. GO enrichment analysis showed that DEGs were enriched in cellular response to cytokines, cytokine-mediated signaling pathway, and regulation of immune cells migration and chemotaxis. KEGG signaling pathway analysis showed that DEGs were mainly involved in cytokine−cytokine receptor interaction, chemokine signaling pathway, and TGF−β signaling pathway. Besides, the mRNA expression levels of SMAD1, SMAD6, CD34, CXCL1, and APLN in the KD group were significantly up-regulated compared with the normal group, whilePITX2 was significantly down-regulated. Conclusion: 102 DEGs in KD serum-induced HCAECs were identified, and six new targets were proposed as potential indicators of KD.

scholarly journals Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

2019 ◽  
Vol 10 (2) ◽  
pp. 443-454
Author(s):  
Chang Liu ◽  
Cornelius Tlotliso Sello ◽  
Yujian Sui ◽  
Jingtao Hu ◽  
Shaokang Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Developmental Stages ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Interaction ◽  
Keratinocyte Proliferation ◽  
Skin Development

In order to enrich the Anser cygnoides genome and identify the gene expression profiles of primary and secondary feather follicles development, de novo transcriptome assembly of skin tissues was established by analyzing three developmental stages at embryonic day 14, 18, and 28 (E14, E18, E28). Sequencing output generated 436,730,608 clean reads from nine libraries and de novo assembled into 56,301 unigenes. There were 2,298, 9,423 and 12,559 unigenes showing differential expression in three stages respectively. Furthermore, differentially expressed genes (DEGs) were functionally classified according to genes ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and series-cluster analysis. Relevant specific GO terms such as epithelium development, regulation of keratinocyte proliferation, morphogenesis of an epithelium were identified. In all, 15,144 DEGs were clustered into eight profiles with distinct expression patterns and 2,424 DEGs were assigned to 198 KEGG pathways. Skin development related pathways (mitogen-activated protein kinase signaling pathway, extra-cellular matrix -receptor interaction, Wingless-type signaling pathway) and genes (delta like canonical Notch ligand 1, fibroblast growth factor 2, Snail family transcriptional repressor 2, bone morphogenetic protein 6, polo like kinase 1) were identified, and eight DEGs were selected to verify the reliability of transcriptome results by real-time quantitative PCR. The findings of this study will provide the key insights into the complicated molecular mechanism and breeding techniques underlying the developmental characteristics of skin and feather follicles in Anser cygnoides.

scholarly journals Electroacupuncture Alleviates Experimental Chronic Inflammatory Pain by Inhibiting Calcium Voltage-Gated Channel-Mediated Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Zhou ◽  
Ying Jin ◽  
Ruijie Ma ◽  
Hongyun Song ◽  
Qin Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Expression Profiles ◽  
Arachidonic Acid Metabolism ◽  
Receptor Interaction ◽  
Bioinformatics Analyses ◽  
Protein Coding ◽  
Chronic Inflammatory Pain ◽  
Gated Channel ◽  
Pathway Analyses

Background. Both experimental and clinical studies have shown that electroacupuncture (EA) administration ameliorates chronic inflammatory pain (CIP). However, the multifaceted mechanism underlying the effects of EA on CIP is poorly understood. In this study, the mRNA transcriptome was used to study various therapeutic targets of EA. Methods. Using RNA-sequencing, protein-coding mRNA expression profiles of the L4-L5 dorsal root ganglion (DRG) were examined in the control (CN), complete Freund’s adjuvant- (CFA-) induced CIP, and EA-treated CIP groups. A series of bioinformatics analyses was performed; “EA-reversed upregulated genes with CIP” (up-DEGs) and “EA-reversed downregulated genes with CIP” (down-DEGs) were identified. Thereafter, based on up-DEGs and down-DEGs, biological functions and signaling pathways were enriched using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. Results. In total, 189 DEGs were identified, including 134 up- and 55 down-DEGs, which were enriched in arachidonic acid metabolism (rno00590), glutamatergic synapse (rno04724), serotonergic synapse (rno04726), FoxO signaling pathway (rno04068), insulin signaling pathway (rno04910), amyotrophic lateral sclerosis (rno05014), cholinergic synapse (rno04725), ECM-receptor interaction (rno04512), and choline metabolism in cancer (rno05231). Conclusion. We identified a few GOs, pathways, and genes that could play key roles in the amelioration of CIP by EA. Hence, this study may provide a theoretical basis for CIP amelioration by EA.

scholarly journals RNA-Seq Reveals the Expression Profiles of Long Non-Coding RNAs in Lactating Mammary Gland from Two Sheep Breeds with Divergent Milk Phenotype

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Signaling Pathway ◽  
Target Genes ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Non Coding Rnas

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.

scholarly journals Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 256
Author(s):  
Annemarie Schwarz ◽  
Ingo Roeder ◽  
Michael Seifert
Keyword(s):  
Gene Expression ◽  
Chronic Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Chronic Phase ◽  
Receptor Interaction ◽  
Similarities And Differences

Chronic myeloid leukemia (CML) is a slowly progressing blood cancer that primarily affects elderly people. Without successful treatment, CML progressively develops from the chronic phase through the accelerated phase to the blast crisis, and ultimately to death. Nowadays, the availability of targeted tyrosine kinase inhibitor (TKI) therapies has led to long-term disease control for the vast majority of patients. Nevertheless, there are still patients that do not respond well enough to TKI therapies and available targeted therapies are also less efficient for patients in accelerated phase or blast crises. Thus, a more detailed characterization of molecular alterations that distinguish the different CML phases is still very important. We performed an in-depth bioinformatics analysis of publicly available gene expression profiles of the three CML phases. Pairwise comparisons revealed many differentially expressed genes that formed a characteristic gene expression signature, which clearly distinguished the three CML phases. Signaling pathway expression patterns were very similar between the three phases but differed strongly in the number of affected genes, which increased with the phase. Still, significant alterations of MAPK, VEGF, PI3K-Akt, adherens junction and cytokine receptor interaction signaling distinguished specific phases. Our study also suggests that one can consider the phase-wise CML development as a three rather than a two-step process. This is in accordance with the phase-specific expression behavior of 24 potential major regulators that we predicted by a network-based approach. Several of these genes are known to be involved in the accumulation of additional mutations, alterations of immune responses, deregulation of signaling pathways or may have an impact on treatment response and survival. Importantly, some of these genes have already been reported in relation to CML (e.g., AURKB, AZU1, HLA-B, HLA-DMB, PF4) and others have been found to play important roles in different leukemias (e.g., CDCA3, RPL18A, PRG3, TLX3). In addition, increased expression of BCL2 in the accelerated and blast phase indicates that venetoclax could be a potential treatment option. Moreover, a characteristic signaling pathway signature with increased expression of cytokine and ECM receptor interaction pathway genes distinguished imatinib-resistant patients from each individual CML phase. Overall, our comparative analysis contributes to an in-depth molecular characterization of similarities and differences of the CML phases and provides hints for the identification of patients that may not profit from an imatinib therapy, which could support the development of additional treatment strategies.

scholarly journals Identification of Key Genes and Pathways Associated with Mast Cells Resting in Meningioma

2020 ◽  
Author(s):  
Hui Xie ◽  
Xiao-hui Ding ◽  
Ce Yuan ◽  
Jin-jiang Li ◽  
Zhao-yang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mast Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Risk Model ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Receptor Interaction ◽  
Key Genes

Abstract Background: To identify candidate key genes and pathways related to mast cells resting in meningioma and the underlying molecular mechanisms of meningioma.Methods: Gene expression profiles of GSE43290 and GSE16581 datasets were obtained from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichments of DEGs were analyzed using the ClusterProfiler package in R. The protein-protein interaction network (PPI), and TF-miRNA- mRNA co-expression networks were constructed. Further, the difference in immune infiltration was investigated using the CIBERSORT algorithm.Results: A total of 1499 DEGs were identified between tumor and normal controls. The analysis of the immune cell infiltration landscape showed that the probability of distribution of memory B cells, regulatory T cells (Tregs), and resting mast cells in tumor samples were significantly higher than those in the controls. Moreover, through WGCNA analysis, the module related to mast cells resting contained 158 DEGs, and KEGG pathway analysis revealed that the DEGs were dominant in the TNF signaling pathway, cytokine-cytokine receptor interaction, and IL-17 signaling pathway. Survival analysis of hub genes related to mast cells resting showed that the risk model was constructed based on 9 key genes. The TF-miRNA- mRNA co-regulation network, including MYC-miR-145-5p, TNFAIP3-miR-29c-3p, and TNFAIP3-hsa-miR-335-3p, were obtained. Further, 36 nodes and 197 interactions in the PPI network were identified. Conclusions: The results of this study revealed candidate key genes, miRNAs, and pathways related to mast cells resting involved in meningioma development, providing potential therapeutic targets for meningioma treatment.

scholarly journals Network Pharmacology-Based Study on the Mechanism of Pinellia ternata in Asthma Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yanmin Lyu ◽  
Xiangjing Chen ◽  
Qing Xia ◽  
Shanshan Zhang ◽  
Chengfang Yao
Keyword(s):  
Candidate Genes ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Th2 Cells ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Pinellia Ternata

Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.

Differential Gene Signature and Signaling Pathways in Childhood Burkitt (BL) vs Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4142-4142
Author(s):  
Nancy S. Day ◽  
Janet Ayello ◽  
Ian Waxman ◽  
Evan Shereck ◽  
Catherine McGuinn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Signal Pathways ◽  
Type I

Abstract The prognosis and treatment of both major forms of advanced childhood B-NHL (BL and DLBCL) is similar with short and intensive multi-agent chemotherapy (Cairo/Patte et al., Blood, 2007 and Patte/Cairo et al., Blood, 2007). Despite both BL and DLBCL being germinal center derived, our recent cytogenetic results of BL vs DLBCL in the FAB LMB 96 study have demonstrated significant differences in secondary chromosomal aberrations in BL vs DLBCL and a differential prognosis based on secondary cytogenetic findings (Poirel/Cairo/Patte, Blood, 2003a). Thus, we sought to identify genes that could uniquely differentiate childhood BL vs DLBCL and discover potential genetic mechanisms of differential molecular pathogenesis and to determine the signal pathways that contribute to the genetic disparity between these two histological types of childhood B-NHL. Nine BL (7 patient samples and 2 cell lines, Raji and Ramos) and 3 DLBCL (1 patient sample and 2 cell lines, Pfeiffer and DB) were compared. Total RNA was isolated, reverse transcribed to cDNA biotinylated cRNA and hybridized to Affymetrix U133A_2 as we have previously described (Jiang/Cairo et al., Journal of Immunology, 2004). Data were analyzed using Agilent GeneSpring 7.3. Signal intensities were compared using one way ANOVA and Welch Test for statistical analysis. Two-fold changes between BL and DLBCL were considered as significant (p<0.05). KEGG Pathways were evaluated for the genes identified. There were 120 genes over-expressed and 217 genes under-expressed in BL vs DLBCL. BL expressed significantly higher level of Ki-67 (a measure of lymphoma-cell proliferation) than DLBCL (2.68F). BL also expressed higher level of the pro-apoptotic gene, p53 compared to DLBCL (1.46F). Over-expressed genes in BL vs DLBCL included TNFSF10 (11.87F), RHOQ (3.16F), PIP5K1B (5.22F) among many others. The genes significantly under-expressed in BL vs DLBCL included PIGL (0.45F), Inositol (myo)-1 (or 4)-monophosphatase 1 (IMPA1; 0.28F), cAMP-dependent regulatory type I, alpha protein kinase (PRKAR1A; 0.37F) among many others. TNFSF10 induces apoptosis in transformed and tumor cells and is known to participate in pathways including cytokine-cytokine receptor interaction and induction of apoptosis through DR3 and DR4/5 death receptors. PIP5K1B is involved in the Rho signaling pathway and PIGL catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis. Since activation of IL3R-mediated cAMP-dependent protein kinase leads to increased cell survival, we searched gene expression profiles in BL vs DLBCL that were involved in IL signaling pathways. The genes that were identified to be over-expressed in BL vs DLBCL included IL2RG (2.24F), IL8RB, IL18 receptor accessory protein (IL18RAP), IL18, IL18R1, and IL1R2 (natural log values of 11.11, 22.95, 2.16, 1.73 and 11.84, respectively in BL vs non-detectable values in DLBCL). Taken together, since IL1, IL2, IL8, and IL18 all belong to IL1 super family, these results suggest significant involvement of TNF (TRAIL) and IL1 super family via cytokine-cytokine receptor interaction and activation of the Rho signaling pathway in Burkitt vs DLBCL lymphomagenesis.

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