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Coronary artery disease susceptibility gene ADTRP regulates cell cycle progression, proliferation, and apoptosis by global gene expression regulation.
Physiol Genomics. 2016 Aug 1;48(8):554-64. doi: 10.1152/physiolgenomics.00028.2016. Epub 2016 May 27.
Luo C1, Wang F2, Qin S1, Chen Q3, Wang QK4.
1The Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, People's Republic of China;
2Department of Molecular Cardiology, Lerner Research Institute, Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; and Department of Molecular Medicine, Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, Ohio qkwang@hust.edu.cn wangq2@ccf.org.
3Department of Molecular Cardiology, Lerner Research Institute, Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; and Department of Molecular Medicine, Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, Ohio.
4The Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Department of Molecular Cardiology, Lerner Research Institute, Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; and Department of Molecular Medicine, Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, Ohio.
Abstract
The ADTRP gene encodes the androgen-dependent TFPI-regulating protein and is a susceptibility gene for contrary artery disease (CAD). We performed global gene expression profiling for ADTRP knock-down using microarrays in human HepG2 cells. Follow-up real-time RT-PCR analysis demonstrated that ADTRP knock-down regulates a diverse set of genes, including upregulation of seven histone genes, downregulation of multiple cell cycle genes (CCND1, CDK4, and CDKN1A), and upregulation of apoptosis genes (CASP7 and PDCD2) in HepG2 cells and endothelial cells. Consistently, ADTRP increases the number of S phase cells during cell cycle, promotes cell proliferation, and inhibits apoptosis. Our study provides novel insights into the function of ADTRP and biological pathways involving ADTRP, which may be involved in the pathogenesis of CAD.
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