scholarly journals Screening and Identification of The Key LncRNAs Associated With Fat Deposition in Ovine Tail

2021 ◽  
Author(s):  
Xiaohui Su ◽  
Haiying He ◽  
Chao Fang ◽  
Lingling Liu ◽  
Wujun Liu
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Critical Role ◽  
Cell Receptor ◽  
Tissue Expression ◽  
Fat Deposition ◽  
Regulatory Function ◽  
Hybrid Population ◽  
Meat Production ◽  
Chemokine Signaling

Abstract Background: Sheep is an important meat-producing animal, and low tail fat deposition level has become one of the main targets of meat production. LncRNAs have recently received special attention due to their critical role in many important biological processes. There are few reports on its regulatory function in ovine fat deposition. In this study, two sheep populations with different tail types in Xinjiang, Bashby sheep (fat-tailed) and the hybrid population of Bashby sheep and wild argali (small-tailed), were selected for whole transcriptome resequencing from their tail tissues. Results: First, 728 differentially expressed lncRNA (DElncRNAs) of tail fat between Bashby and F2 sheep were identified by RNA-seq. Second, the tissue expression profile and relative expression difference between Bashby and F2 sheep of 7 of 728 DE lncRNAs were analyzed by RT-PCR. We conclude that MSTRG.37980, MSTRG.38164, MSTRG.36912 and MSTRG.36913 positively regulate fat deposition, while MSTRG.8169, MSTRG.24995 and MSTRG.31389 inhibit fat deposition. Third, GO and KEGG analysis revealed that lncRNA targets were mainly participated in energy metabolism, growth and development and immunity, such as viral carcinogenesis, Chemokine signaling pathway, B cell receptor signaling pathway. And the expression pattern of target genes in each tissue was similar to that of the corresponding lncRNAs, which required us to conduct further research on target genes. Conclusions: This study was the first to systematically identify fat deposition-associated lncRNAs in ovine tail fat and construct DElncRNAs profiles. Our findings will help understand the molecular mechanism of fat deposition from transcriptomic perspectives.

scholarly journals Ibrutinib in B-cell lymphoma: single fighter might be enough?

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Xue ◽  
Xin Wang ◽  
Lingyan Zhang ◽  
Qingyuan Qu ◽  
Qian Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
High Response Rate ◽  
Main Body ◽  
Combination Strategies ◽  
Bcr Signaling

Abstract Background In recent years, the B cell receptor (BCR) signaling pathway has become a “hot point” because it plays a critical role in B-cell proliferation and function. Bruton’s tyrosine kinase (BTK) is overexpressed in many subtypes of B-cell lymphoma as a downstream kinase in the BCR signaling pathway. Ibrutinib, the first generation of BTK inhibitor, has shown excellent antitumor activity in both indolent and aggressive B-cell lymphoma. Main body Ibrutinib monotherapy has been confirmed to be effective with a high response rate (RR) and well-tolerated in many B-cell lymphoma subgroups. To achieve much deeper and faster remission, combination strategies contained ibrutinib were conducted to evaluate their synergistic anti-tumor effect. Conclusions For patients with indolent B-cell lymphoma, most of them respond well with ibrutinib monotherapy. Combination strategies contained ibrutinib might be a better choice to achieve deeper and faster remission in the treatment of aggressive subtypes of B-cell lymphoma. Further investigations on the long-term efficacy and safety of the ibrutinib will provide novel strategies for individualized treatment of B-cell lymphoma.

scholarly journals Critical role of PI3K signaling for NF-κB–dependent survival in a subset of activated B-cell–like diffuse large B-cell lymphoma cells

2010 ◽  
Vol 108 (1) ◽  
pp. 272-277 ◽  
Author(s):  
Bernhard Kloo ◽  
Daniel Nagel ◽  
Matthias Pfeifer ◽  
Michael Grau ◽  
Michael Düwel ◽  
...  
Keyword(s):  
B Cell ◽  
Target Genes ◽  
Cell Lymphoma ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Critical Function ◽  
Large B Cell Lymphoma ◽  
Bcr Signaling ◽  
Large B Cell

The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 protease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.

scholarly journals Specific Differentially Methylated and Expressed Genes in People with Longevity Family History

2021 ◽  
Author(s):  
Chunhong LI ◽  
Qingqing NONG ◽  
Bin GUAN ◽  
Haoyu HE ◽  
Zhiyong ZHANG
Keyword(s):  
Family History ◽  
Signaling Pathway ◽  
Killer Cell ◽  
Cell Receptor ◽  
Human Longevity ◽  
Chemokine Signaling ◽  
Differentially Methylated Genes ◽  
Receptor Signaling Pathway ◽  
Chemokine Signaling Pathway ◽  
And Control

Background: We attempt to identify specific differentially methylated and expressed genes in people with longevity family history, it will contribute to discover significant features about human longevity. Methods: A prevalence study was conducted during October 2017 to January 2019 in Bama County of Guangxi, China and individuals were recruited and grouped into longevity family (n=60) and non-longevity family (n=60) to identify differentially methylated genes (DMGs). The expression profile dataset GSE16717 was downloaded from the GEO database in which individuals were divided into 3 groups, namely longevity (n=50), longevity offspring (n=50) and control (n=50) for identifying differentially expressed genes (DEGs). It was considered significantly different when P or adjusted P0.05. Results: In total, 117 longevity-related hypermethylated genes enriched in interleukin secretion/production regulation, chemokine signaling pathway and natural killer cell-mediated cytotoxicity. Another 296 significant key longevity-related DEGs primarily involved in protein binding, nucleus, cytoplasm, T cell receptor signaling pathway and Metabolic pathway, H19 and PFKFB4 were found to be both methylated and downregulated in people with longevity family history. Conclusion: Human longevity-specific genes involve in many immunity regulations and cellular immunity pathways, H19 and PFKFB4 show hypermethylated and suppressed status in people with longevity family history and might serve as longevity candidate genes.

scholarly journals Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis

2016 ◽  
Vol 101 (4) ◽  
pp. 1552-1561 ◽  
Author(s):  
Yong Song ◽  
Jing Fu ◽  
Min Zhou ◽  
Li Xiao ◽  
Xue Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Stromal Cells ◽  
Target Genes ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Endometrial Stromal Cells ◽  
Proliferation And Apoptosis

Abstract Context: The imbalance in cell proliferation and apoptosis is considered an important role in the pathogenesis of endometriosis, but the exact mechanisms remains unclear. A newly established signaling pathway–Hippo/Yes-associated protein (YAP) pathway plays a critical role in the proliferation and apoptosis processes. However, studies focusing on Hippo/YAP pathway and endometriosis are lacking. Objective: The objective was to explore the function of the Hippo/YAP pathway in endometriosis. Setting and Design: The expression of YAP was first investigated in endometrium of women with or without endometriosis. The role of YAP in cell proliferation and apoptosis is identified by transfection of endometrial stromal cells (ESCs) in vitro, subsequent Verteporfin treatments in eutopic ESCs in vitro, and endometriosis animal model of nude mice in vivo. Results: Our results revealed that increased expression of YAP and decreased expression of p-YAP in ectopic and eutopic endometrium compared with normal endometrium. YAP knockdown in eutopic ESCs decreased cell proliferation and enhanced cell apoptosis companied with decreased expression of TEAD1, CTGF, and B-cell lymphoma/leukemia (BCL)-2; whereas overexpression of YAP resulted in increased proliferation and decreased apoptosis of normal ESCs with increased expression of TEAD1, CTGF, and BCL-2. By chromatin immunoprecipitation qPCR CTGF and BCL-2 were identified as directly downstream target genes of YAP-TEAD1 active complex. Eutopic ESCs treated with Verteporfin revealed decreased proliferation and enhanced apoptosis whereas in endometriosis animal models of nude mice treated with Verteporfin, the size of endometriotic lesions was significantly reduced. Conclusions: Our study suggests that the Hippo/YAP-signaling pathway plays a critical role in the pathogenesis of endometriosis and should present a novel therapeutic method against endometriosis.

scholarly journals Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ferah Budak ◽  
Salih Haldun Bal ◽  
Gulcin Tezcan ◽  
Halis Akalın ◽  
Guher Goral ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Acute Infection ◽  
Mapk Signaling ◽  
Receptor Interaction ◽  
Chronic Infections ◽  
Peripheral Blood Mononuclear ◽  
Mirna Array ◽  
Chemokine Signaling

Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p<0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

scholarly journals Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Siyi Zhang ◽  
Bo Wang ◽  
Jingsong Shi ◽  
Jing Li
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

scholarly journals HDAC1 regulates the chromatin landscape to establish transcriptional dependencies in chronic lymphocytic leukemia

2020 ◽  
Author(s):  
Tzung-Huei Lai ◽  
Hatice Gulcin Ozer ◽  
Pierluigi Gasparini ◽  
Giovanni Nigita ◽  
Rosario Destefano ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Target Genes ◽  
Critical Role ◽  
Cell Receptor ◽  
Chromatin Accessibility ◽  
Lymphocytic Leukemia ◽  
Hdac Inhibition ◽  
Driver Genes ◽  
Transcriptional Dysregulation

AbstractHDAC1 is a key regulator of gene expression in cancer. We identified a critical role for HDAC1 in establishing the transcriptional dependencies essential for survival in chronic lymphocytic leukemia (CLL) by profiling HDAC1 with BRD4, H3K27Ac superenhancers, H4K9Ac, chromatin accessibility signatures, Pol2 measurements and expression signatures to generate a regulatory chromatin landscape. Superenhancers marked by high levels of acetylation and BRD4 paradoxically also recruited the highest levels of HDAC1. HDAC inhibition poisoned transcription at these loci to selectively disrupt B-cell transcription factors and B-cell receptor signaling. HDAC1 was also recruited genome-wide at promoters without superenhancers to repress expression; HDAC inhibition induces these genes which include key microRNA networks that reciprocally downregulate CLL specific survival and driver genes. Our work provides a compelling rationale for profiling HDAC1 across cancers to characterize its role in driving the transcriptional dysregulation that is a hallmark of most cancers and develop epigenetic therapeutic strategies.SignificanceOur work definitively establishes the composition of the regulatory chromatin that enables HDAC1 to function as an activator and repressor at distinct target genes within the same tumor to drive transcriptional dysregulation and allow the expression of B cell specific signaling and survival networks that are critical for survival.

scholarly journals Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3137
Author(s):  
Juan Pablo Rigalli ◽  
Dirk Theile ◽  
Julie Nilles ◽  
Johanna Weiss
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Chromatin Condensation ◽  
Critical Role ◽  
Pregnane X Receptor ◽  
Histone Deacetylation ◽  
Regulatory Function ◽  
Mediated Effects ◽  
Cancer Pathogenesis

The pregnane X receptor (PXR, NR1I2) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, NR2B1) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the regulation of drug metabolism and excretion, metabolic and immunological functions and cancer pathogenesis. PXR activity is strongly regulated by the association with coactivator and corepressor proteins. Coactivator proteins exhibit histone acetyltransferase or histone methyltransferase activity or associate with proteins having one of these activities, thus promoting chromatin decondensation and activation of the gene expression. On the contrary, corepressor proteins promote histone deacetylation and therefore favor chromatin condensation and repression of the gene expression. Several studies pointed to clear cell- and ligand-specific differences in the activation of PXR. In this article, we will review the critical role of coactivator and corepressor proteins as molecular determinants of the specificity of PXR-mediated effects. As already known for other nuclear receptors, understanding the complex mechanism of PXR activation in each cell type and under particular physiological and pathophysiological conditions may lead to the development of selective modulators with therapeutic potential.

scholarly journals Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 337
Author(s):  
Annah Lee ◽  
Gabriela Cardoso Dal Pont ◽  
Michele Battaglia ◽  
Ryan J. Arsenault ◽  
Michael H. Kogut
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Immune Modulation ◽  
Cell Receptor ◽  
Host Immunity ◽  
Broiler Chicks ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway ◽  
Stat Pathway

The objective of this study was to identify the phosphorylation events associated with host immunity with the inclusion of chestnut tannins (ChT) in the diet. A total of 200 male day-of-hatch Cobb 500 chicks were randomly assigned to two treatment groups, totaling 50 chicks per pen per experiment (this study was repeated two times). The treatments were as follows: (1) control feed—normal starter feed (n = 50), and (2) 1% ChT inclusion feed (n = 50). The ceca were collected on each necropsy day for analysis via (1) a peptide array to provide tissue immunometabolism information from the host, and (2) quantitative PCR for mRNA expression. Of the top three immune pathways, the data identified the T-cell receptor signaling pathway, the chemokine signaling pathway, and the JAK-STAT signaling pathway. The results showed significantly altered phosphorylation of JAK and STAT peptides within the JAK-STAT pathway. These results support the mRNA expression data with the upregulated IL-6 response, due to the significant phosphorylation of IL6ST, JAK, and STAT peptides. In regard to immune modulation, ChT appear to influence host immunity via an IL-6 mediated response which could be beneficial in host defenses against pathogens at the early stages of broiler growth and development. Therefore, it is suggested that the role of the JAK-STAT pathway is altered by including ChT in the diet.

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