scholarly journals MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia

2020 ◽  
Vol 11 ◽  
Author(s):  
Geysson Javier Fernandez ◽  
Juarez Henrique Ferreira ◽  
Ivan José Vechetti ◽  
Leonardo Nazario de Moraes ◽  
Sarah Santiloni Cury ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

scholarly journals MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia

2019 ◽  
Author(s):  
Geysson Javier Fernandez ◽  
Juarez Henrique Ferreira ◽  
Ivan José Vechetti-Júnior ◽  
Leonardo Nazario de Moraes ◽  
Sarah Santiloni Cury ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Cancer Cachexia ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
C2c12 Myotubes ◽  
Transcriptional Regulatory Networks ◽  
Necrosis Factor Alpha ◽  
Transcriptional Regulatory ◽  
Post Transcriptional Regulation

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

2021 ◽  
Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Progesterone Receptors ◽  
Activator Protein 1 ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Pathways ◽  
Transcriptional Regulatory ◽  
Mechanistic Basis ◽  
Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

scholarly journals Transcriptional Regulatory Networks Associate with Early Stages of Potato Virus X Infection of Solanum tuberosum

2021 ◽  
Vol 22 (6) ◽  
pp. 2837
Author(s):  
Venura Herath ◽  
Jeanmarie Verchot
Keyword(s):  
Potato Virus ◽  
Regulatory Networks ◽  
Potato Virus X ◽  
Early Response ◽  
Pathogen Resistance ◽  
Transcriptional Regulatory Networks ◽  
Unfolded Protein ◽  
Molecular Pattern ◽  
Transcriptional Regulatory ◽  
Protein Response

Potato virus X (PVX) belongs to genus Potexvirus. This study characterizes the cellular transcriptome responses to PVX infection in Russet potato at 2 and 3 days post infection (dpi). Among the 1242 differentially expressed genes (DEGs), 268 genes were upregulated, and 37 genes were downregulated at 2 dpi while 677 genes were upregulated, and 265 genes were downregulated at 3 dpi. DEGs related to signal transduction, stress response, and redox processes. Key stress related transcription factors were identified. Twenty-five pathogen resistance gene analogs linked to effector triggered immunity or pathogen-associated molecular pattern (PAMP)-triggered immunity were identified. Comparative analysis with Arabidopsis unfolded protein response (UPR) induced DEGs revealed genes associated with UPR and plasmodesmata transport that are likely needed to establish infection. In conclusion, this study provides an insight on major transcriptional regulatory networked involved in early response to PVX infection and establishment.

scholarly journals The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Chen ◽  
Shirley Luo ◽  
Abigail Dupre ◽  
Roshan P. Vasoya ◽  
Aditya Parthasarathy ◽  
...  
Keyword(s):  
Brush Border ◽  
Regulatory Networks ◽  
Critical Role ◽  
Yolk Sac ◽  
Apical Surface ◽  
Transcriptional Regulatory Networks ◽  
Chromatin Looping ◽  
Multiple Organs ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

AbstractThe brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood. Here, we identify that hepatocyte nuclear factor 4 (HNF4) transcription factor is a conserved and important regulator of brush border gene program in multiple organs, such as intestine, kidney and yolk sac. Compromised brush border gene signatures and impaired transport were observed in these tissues upon HNF4 loss. By ChIP-seq, we find HNF4 binds and activates brush border genes in the intestine and kidney. H3K4me3 HiChIP-seq identifies that HNF4 loss results in impaired chromatin looping between enhancers and promoters at gene loci of brush border genes, and instead enhanced chromatin looping at gene loci of stress fiber genes in the intestine. This study provides comprehensive transcriptional regulatory mechanisms and a functional demonstration of a critical role for HNF4 in brush border gene regulation across multiple murine epithelial tissues.

scholarly journals Flynet: a genomic resource for Drosophila melanogaster transcriptional regulatory networks

2009 ◽  
Vol 25 (22) ◽  
pp. 3001-3004 ◽  
Author(s):  
F. Tian ◽  
P. K. Shah ◽  
X. Liu ◽  
N. Negre ◽  
J. Chen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Genomic Resource

Transcriptional regulatory networks evoked by both flow and pharmacophores that confer endothelial atheroprotection

2006 ◽  
Vol 45 (3) ◽  
pp. e47
Author(s):  
Kush M. Parmar ◽  
H. Benjamin Larman ◽  
Vinod Nambudiri ◽  
Guohao Dai ◽  
Yuzhi Zhang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory
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