scholarly journals The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation

2021 ◽  
Vol 8 ◽  
Author(s):  
Linyuan Huang ◽  
Jun Zhang ◽  
Xinyun Zhu ◽  
Xue Mi ◽  
Qiujie Li ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Small Subset ◽  
Messenger Rnas ◽  
Demethylase Activity ◽  
Differential Gene ◽  
Gene Regulatory ◽  
Novel Target ◽  
Therapeutic Research ◽  
Dose Dependent ◽  
Mechanistic View

Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research.

scholarly journals Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue

2021 ◽  
Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Hot Spot ◽  
Genetic Research ◽  
Noncoding Rnas ◽  
Messenger Rnas ◽  
Effective Prevention ◽  
Gene Regulatory ◽  
The Relationship

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

scholarly journals Differential Co-Expression Analyses Allow the Identification of Critical Signalling Pathways Altered during Tumour Transformation and Progression

2020 ◽  
Vol 21 (24) ◽  
pp. 9461
Author(s):  
Aurora Savino ◽  
Paolo Provero ◽  
Valeria Poli
Keyword(s):  
Cancer Biology ◽  
Regulatory Networks ◽  
Tumour Progression ◽  
External Perturbation ◽  
Data Types ◽  
Differential Gene ◽  
Gene Regulatory ◽  
Experimental Validations ◽  
Definition Of ◽  
Future Work

Biological systems respond to perturbations through the rewiring of molecular interactions, organised in gene regulatory networks (GRNs). Among these, the increasingly high availability of transcriptomic data makes gene co-expression networks the most exploited ones. Differential co-expression networks are useful tools to identify changes in response to an external perturbation, such as mutations predisposing to cancer development, and leading to changes in the activity of gene expression regulators or signalling. They can help explain the robustness of cancer cells to perturbations and identify promising candidates for targeted therapy, moreover providing higher specificity with respect to standard co-expression methods. Here, we comprehensively review the literature about the methods developed to assess differential co-expression and their applications to cancer biology. Via the comparison of normal and diseased conditions and of different tumour stages, studies based on these methods led to the definition of pathways involved in gene network reorganisation upon oncogenes’ mutations and tumour progression, often converging on immune system signalling. A relevant implementation still lagging behind is the integration of different data types, which would greatly improve network interpretability. Most importantly, performance and predictivity evaluation of the large variety of mathematical models proposed would urgently require experimental validations and systematic comparisons. We believe that future work on differential gene co-expression networks, complemented with additional omics data and experimentally tested, will considerably improve our insights into the biology of tumours.

scholarly journals Differential gene regulatory pathways and co-expression networks associated with fire blight infection in apple (Malus × domestica)

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Katchen Julliany Pereira Silva ◽  
Jugpreet Singh ◽  
Ryland Bednarek ◽  
Zhangjun Fei ◽  
Awais Khan
Keyword(s):  
Malus Domestica ◽  
Fire Blight ◽  
Regulatory Pathways ◽  
Differential Gene ◽  
Gene Regulatory

scholarly journals Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013 ◽  
Vol 12 (9) ◽  
pp. 1293-1304 ◽  
Author(s):  
Anda Zhang ◽  
Zhongle Liu ◽  
Lawrence C. Myers
Keyword(s):  
Candida Albicans ◽  
Ectopic Expression ◽  
Small Subset ◽  
Content Type ◽  
Impaired Ability ◽  
Transcriptional Effect ◽  
Environmental Induction ◽  
Gene Regulatory ◽  
The Stability ◽  
Negative Gene

ABSTRACT The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual deletions of eight C. albicans Mediator subunits have shown that different Mediator subunits have dramatically diverse effects on the directionality, frequency, and environmental induction of epigenetic switching. Among the Mediator deletion mutants analyzed, only Med12 has a steady-state transcriptional effect on the components of the Wor1 circuit that clearly corresponds to its effect on switching. The MED16 and MED9 genes have been found to be among a small subset of genes that are required for the stability of both the white and opaque states. Deletion of the Med3 subunit completely destabilizes the opaque state, even though the Wor1 transcription circuit is intact and can be driven by ectopic expression of Wor1. The highly impaired ability of the med3 deletion mutant to mate, even when Wor1 expression is ectopically induced, reveals that the activation of the Wor1 circuit can be decoupled from the opaque state and one of its primary biological consequences.

IKKα as a potential novel target for treatment of colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 174-174
Author(s):  
Jean A. Quinn ◽  
Meera Patel ◽  
Kathryn AF Pennel ◽  
Dustin Flanagan ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Mouse Models ◽  
Dependent Manner ◽  
Cancer Specific Survival ◽  
Similar Reduction ◽  
Novel Target ◽  
Dose Dependent ◽  
Tumour Differentiation

174 Background: Colorectal cancer (CRC) is a heterogeneous disease leading to different survival outcomes for patients with the same stage of disease. The non-canonical NF-κB pathway has been shown to have a key role in tumorigenesis, and the aim of this study was to investigate the role of IKKα, the main catalytic component of this pathway in CRC. Methods: A tissue microarray was retrospectively constructed from a patient cohort (1033) with stage I-III CRC who underwent surgery. IHC was utilised to examine cytoplasmic and punctate IKKα expression and determine any association with clincopathological features and cancer specific survival (CSS). To assess IKKα inhibition, organoids were prepared from wild type (WT) mouse colon, mouse models of CRC (Apc and Apc.KRAS.pT53.TGFbR2 (AKPT)) and patient derived human organoids. These were treated with an IKKα inhibitor, SU1433 and organoid size and cell viability assessed. Results: High cytoplasmic expression of IKKα was associated with increasing T stage (p = 0.012), poor tumour differentiation (p = 0.010), tumour necrosis (p = 0.013) and low proliferation status (p = 0.013) but was not associated with CSS. High punctate IKKα expression associated with tumour differentiation (p = 0.001), necrosis (p = 0.004), proliferation (p = 0.044) and MMR competence (p < 0.001) and was also significantly associated with reduced CSS (HR1.20 95%CI 1.02-1.42, p < 0.001). SU1433 did not significantly impact on WT (C57/B16) organoid viability up to a concentration of 1 uM, however organoid size and cell viability was significantly reduced in a dose dependent manner in organoids from both Apc and AKPT mouse models. A similar reduction was observed in patient derived human organoids. Conclusions: Punctate IKKα expression was associated with poor cancer specific survival in CRC patients, and inhibition with SU1433, impacted on CRC mouse and patient derived human organoid size and cell viability. These results suggest that, following further investigation and confirmation, IKKα may be employed as a novel therapeutic target in CRC.

Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray

2007 ◽  
Vol 32 (1) ◽  
pp. 33-44 ◽  
Author(s):  
S. A. M. Martin ◽  
J. B. Taggart ◽  
P. Seear ◽  
J. E. Bron ◽  
R. Talbot ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Cell Line ◽  
Host Response ◽  
Transcriptional Response ◽  
Pcr Analysis ◽  
Type I ◽  
Type Ii ◽  
Type I Ifns ◽  
A Cell ◽  
Differential Gene

Interferons (IFNs) are cytokines that have proinflammatory, antiviral, and immunomodulatory effects and play a central role during a host response to pathogens. The IFN family contains both type I and type II molecules. While there are a number of type I IFNs, there is only one type II IFN. Recently both type I and type II IFN genes have been cloned in salmonid fish and recombinant proteins produced showing IFN activity. We have stimulated an Atlantic salmon cell line (SHK-1) with both type I and type II recombinant salmonid IFNs and analyzed the transcriptional response by microarray analysis. Cells were exposed to recombinant IFNs for 6 or 24 h or left unexposed as controls. RNA was hybridized to an Atlantic salmon cDNA microarray (salmon 17K feature TRAITS/SGP array) in order to assess differential gene expression in response to IFN exposure. For IFN I and II, 47 and 72 genes were stimulated, respectively; most genes were stimulated by a single IFN type, but some were affected by both IFNs, indicating coregulation of the IFN response in fish. Real-time PCR analysis was employed to confirm the microarray results for selected differentially expressed genes in both a cell line and primary leukocyte cultures.

scholarly journals Dose-Dependent Effects of Dietary Fat on Development of Obesity in Relation to Intestinal Differential Gene Expression in C57BL/6J Mice

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e19145 ◽  
Author(s):  
Nicole J. W. de Wit ◽  
Mark V. Boekschoten ◽  
Eva-Maria Bachmair ◽  
Guido J. E. J. Hooiveld ◽  
Philip J. de Groot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Dietary Fat ◽  
Differential Gene ◽  
Dose Dependent

scholarly journals Gi proteins mediate activation of the canonical hedgehog pathway in the myocardium

2014 ◽  
Vol 307 (1) ◽  
pp. H66-H72 ◽  
Author(s):  
Christian J. Carbe ◽  
Lan Cheng ◽  
Sankar Addya ◽  
Jessica I. Gold ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Purinergic Signaling ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Transcriptional Response ◽  
Neonatal Rat ◽  
Small Subset ◽  
Dependent Manner ◽  
Gli1 Expression ◽  
Ventricular Cardiomyocytes ◽  
First Time

During myocardial ischemia, upregulation of the hedgehog (Hh) pathway promotes neovascularization and increases cardiomyocyte survival. The canonical Hh pathway activates a transcriptional program through the Gli family of transcription factors by derepression of the seven-transmembrane protein smoothened (Smo). The mechanisms linking Smo to Gli are complex and, in some cell types, involve coupling of Smo to Gi proteins. In the present study, we investigated, for the first time, the transcriptional response of cardiomyocytes to sonic hedgehog (Shh) and the role of Gi protein utilization. Our results show that Shh strongly activates Gli1 expression by quantitative PCR in a Smo-dependent manner in neonatal rat ventricular cardiomyocytes. Microarray analysis of gene expression changes elicited by Shh and sensitive to a Smo inhibitor identified a small subset of 37 cardiomyocyte-specific genes regulated by Shh, including some in the PKA and purinergic signaling pathways. In addition, neonatal rat ventricular cardiomyocytes infected with an adenovirus encoding GiCT, a peptide that impairs receptor-Gi protein coupling, showed reduced activation of Hh targets. In vitro data were confirmed in transgenic mice with cardiomyocyte-inducible GiCT expression. Transgenic GiCT mice showed specific reduction of Gli1 expression in the heart under basal conditions and failed to upregulate the Hh pathway upon ischemia and reperfusion injury, unlike their littermate controls. This study characterizes, for the first time, the transcriptional response of cardiomyocytes to Shh and establishes a critical role for Smo coupling to Gi in Hh signaling in the normal and ischemic myocardium.

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