ArticleBiochimica et biophysica acta. Molecular basis of disease2017
Identification of a molecular signaling gene-gene regulatory network between GWAS susceptibility genes ADTRP and MIA3/TANGO1 for coronary artery disease.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- The Emerging Role of Mechanobiology in Connecting Metabolic and Cardiovascular Diseases: From Fundamentals to Future Therapies.Biomedicines · 2026Review
- AIG1 protects against doxorubicin-induced cardiomyocyte ferroptosis and cardiotoxicity by promoting ubiquitination-mediated p53 degradation.Theranostics · 2025Article
- MIA3 promotes the degradation of GSH (glutathione) by binding to CHAC1, thereby promoting the progression of hepatocellular carcinoma.Molecular and cellular biochemistry · 2024Article
- Applications of Genome Editing Technologies in CAD Research and Therapy with a Focus on Atherosclerosis.International journal of molecular sciences · 2023Review
- AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling.Nature communications · 2023Article
- Androgen-dependent tissue factor pathway inhibitor regulating protein: a review of its peripheral actions and association with cardiometabolic diseases.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Receptor and Molecular Mechanism of AGGF1 Signaling in Endothelial Cell Functions and Angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Molecular Phylogenetic Analysis of theGenes · 2021Article
- GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele.Molecular genetics and genomics : MGG · 2021Article
- Insights into the Functional Role of ADTRP (Androgen-Dependent TFPI-Regulating Protein) in Health and Disease.International journal of molecular sciences · 2021Review
- Angiogenic factor AGGF1 acts as a tumor suppressor by modulating p53 post-transcriptional modifications and stability via MDM2.Cancer letters · 2021Article
- MIA SH3 Domain ER Export Factor 3 Deficiency Prevents Neointimal Formation by Restoring BAT-Like PVAT and Decreasing VSMC Proliferation and Migration.Frontiers in endocrinology · 2021Article
- Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.Circulation research · 2020Article
- Splice variants of lncRNA RNA ANRIL exert opposing effects on endothelial cell activities associated with coronary artery disease.RNA biology · 2020Article
- Statistical and Functional Studies Identify Epistasis of Cardiovascular Risk Genomic Variants From Genome-Wide Association Studies.Journal of the American Heart Association · 2020Article
- ADAMTS16 activates latent TGF-β, accentuating fibrosis and dysfunction of the pressure-overloaded heart.Cardiovascular research · 2020Article
- Article
- Endoplasmic reticulum quality control in lipoprotein metabolism.Molecular and cellular endocrinology · 2019Review
- UBC9 regulates cardiac sodium channel NaJournal of molecular and cellular cardiology · 2019Article
- Long noncoding RNAThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Coronary artery disease (CAD) is the leading cause of death worldwide. GWAS have identified >50 genomic loci for CAD, including ADTRP and MIA3/TANGO1. However, it is important to determine whether the GWAS genes form a molecular network. In this study, we have uncovered a novel molecular network between ADTRP and MIA3/TANGO1 for the pathogenesis of CAD. We showed that knockdown of ADTRP expression markedly down-regulated expression of MIA3/TANGO1. Mechanistically, ADTRP positively regulates expression of PIK3R3 encoding the regulatory subunit 3 of PI3K, which leads to activation of AKT, resulting in up-regulation of MIA3/TANGO1. Both ADTRP and MIA3/TANGO1 are involved in endothelial cell (EC) functions relevant to atherosclerosis. Knockdown of ADTRP expression by siRNA promoted oxidized-LDL-mediated monocyte adhesion to ECs and transendothelial migration of monocytes, inhibited EC proliferation and migration, and increased apoptosis, which was reversed by expression of constitutively active AKT1 and MIA3/TANGO1 overexpression, while the over-expression of ADTRP in ECs blunted these processes. Knockdown of MIA3/TANGO1 expression also promoted monocyte adhesion to ECs and transendothelial migration of monocytes, and vice versa for overexpression of MIA3/TANGO1. We found that ADTRP negatively regulates the levels of collagen VII and ApoB in HepG2 and endothelial cells, which are downstream regulatory targets of MIA3/TANGOI. In conclusion, we have uncovered a novel molecular signaling pathway for the pathogenesis of CAD, which involves a novel gene-gene regulatory network. We show that ADTRP positively regulates PIK3R3 expression, which leads to activation of AKT and up-regulation of MIA3/TANGO1, thereby regulating endothelial cell functions directly relevant to atherosclerosis.
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