Topics

Co-expression network analysis identified hub genes critical to triglyceride and free fatty acid metabolism as key regulators of age-related vascular dysfunction in mice.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Co-expression network analysis identified hub genes critical to triglyceride and free fatty acid metabolism as key regulators of age-related vascular dysfunction in mice."

Aging has often been linked to age-related vascular disorders. The elucidation of the putative genes and pathways underlying vascular aging likely provides useful insights into vascular diseases at advanced ages. Transcriptional regulatory network analysis is the key to describing genetic interactions between molecular regulators and their target gene transcriptionally changed during vascular aging. A total of 469 differentially expressed genes were parsed into 6 modules. Among the incorporated sample traits, the most significant module related to vascular aging was associated with triglyceride and enriched with biological terms like proteolysis, blood circulation, and circulatory system process. The module associated with triglyceride was preserved in an independent microarray dataset, indicating the robustness of the identified vascular aging-related subnetwork. Additionally, Enpp5, Fez1, Kif1a, F3, H2-Q7, and their interacting miRNAs mmu-miR-449a, mmu-miR-449c, mmu-miR-34c, mmu-miR-34b-5p, mmu-miR-15a, and mmu-let-7, exhibited the most connectivity with external lipid-related traits. Transcriptional alterations of the hub genes Enpp5, Fez1, Kif1a, and F3, and the interacting microRNAs mmu-miR-34c, mmu-miR-34b-5p, mmu-let-7, mmu-miR-449a, and mmu-miR-449c were confirmed. Our findings demonstrate that triglyceride and free fatty acid-related genes are key regulators of age-related vascular dysfunction in mice and show that the hub genes for Enpp5, Fez1, Kif1a, and F3 as well as their interacting miRNAs mmu-miR-34c, mmu-miR-34b-5p, mmu-let-7, mmu-miR-449a, and mmu-miR-449c, could serve as potential biomarkers in vascular aging. The microarray gene expression profiles of aorta samples from 6-month old mice (n=6) and 20-month old mice (n=6) were processed to identify nominal differentially expressed genes. These nominal differentially expressed genes were subjected to a weighted gene co-expression network analysis. A network-driven integrative analysis with microRNAs and transcription factors was performed to define significant modules and underlying regulatory pathways associated with vascular aging, and module preservation test was conducted to validate the age-related modules based on an independent microarray gene expression dataset in mice aorta samples including three 32-week old wild-type mice (around 6-month old) and three 78-week old wild-type mice (around 20-month old). Gene ontology and protein-protein interaction analyses were conducted to determine the hub genes as potential biomarkers in the progress of vascular aging. The hub genes were further validated with quantitative real-time polymerase chain reaction in aorta samples from 20 young (6-month old) mice and 20 old (20-month old) mice.

Affiliation

Journal Details

This article was published in the following journal.

Name: Aging
ISSN: 1945-4589
Pages:

Links

DeepDyve research library

PubMed Articles [44794 Associated PubMed Articles listed on BioPortfolio]

Identifying gene modules of thyroid cancer associated with pathological stage by weighted gene co-expression network analysis.

Thyroid cancer is the most common type of endocrine tumor. The TNM classification remains a standard for treatment determination and predicting prognosis in thyroid cancer. The genes modules associate...

Construction and analysis of gene co-expression networks in intracranial aneurysm.

To analyze the expression microarray data in the public databases of intracranial aneurysms (IA) using bioinformatics, and to provide important information for the study of disease mechanisms. Gene c...

Identification of biomarkers correlated with hypertrophic cardiomyopathy with co-expression analysis.

Hypertrophic cardiomyopathy (HCM) is reported to be the most common genetic heart disease. To identify key module and candidate biomarkers correlated with clinical prognosis of patients with HCM, we c...

Co-expression network analysis identified candidate biomarkers in association with progression and prognosis of breast cancer.

Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. Weighted gene co-expression network analysis was used to co...

Exploring the involvement of Tac2 in the mouse hippocampal stress response through gene networking.

Tac2 is expressed in a number of areas throughout the brain, including the hippocampus. However, knowledge about its function has been only well explored in the hypothalamus in the context of reproduc...

Clinical Trials [11042 Associated Clinical Trials listed on BioPortfolio]

Microarray Analysis of Gene Expression and Identification of Progenitor Cells in Lung Carcinoma

This study will investigate gene expression profiles in normal human lung tissue, lung carcinoma and metastatic tumor to the lung. The expression of up to 20,000 genes in a given lung tis...

Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

RATIONALE: Studying samples of bone marrow or blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers rela...

Observational Study Analyzing RNA Expression of Endometrial Biopsy Samples From Placebo, Bazedoxifene/Conjugated Estroge

This study is an observational study analyzing the biopsy samples collected from subjects that participated in Study 3115A1-303 (NCT00675688). These endometrial biopsy samples will be de-...

TRANSCRIBE (Transcriptomic Analysis of Left Ventricular Gene Expression)

Hypothesis: The investigators hypothesize that genetic variants will alter gene expression in response to ischemia during cardiopulmonary bypass. To test this, the investigators will be ta...

Evaluating Genes in Sputum to Measure Drug Response in COPD

The purpose of this research study is to determine whether analysis of genes in sputum is a useful noninvasive technique for measuring response to drugs in patients with COPD. We propose ...

Medical and Biotech [MESH] Definitions

A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.

Meta-analysis of randomized trials in which estimates of comparative treatment effects are visualized and interpreted from a network of interventions that may or may not have been evaluated directly against each other. Common considerations in network meta-analysis include conceptual and statistical heterogeneity and incoherence.

Y-box-binding protein 1 was originally identified as a DNA-binding protein that interacts with Y-box PROMOTER REGIONS of MHC CLASS II GENES. It is a highly conserved transcription factor that regulates expression of a wide variety of GENES.

Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.

An antennapedia-like homeodomain transcription factor that regulates the expression of multiple genes in the INTESTINAL MUCOSA. It plays a critical role in many processes from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine.

Quick Search


DeepDyve research library

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Vascular
Vascular relates to blood vessels (Oxford Medical Dictionary) and can be used to describe the supply of blood, a disease affecting the blood vessels or molecules associated with these structures. For example, <!--LGfEGNT2Lhm-->atherosclerosis ...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article