Research Papers:
Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210
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Abstract
Ku-Chung Chen1, Yi-Chu Liao2,3, Jaw-Yuan Wang4,5,6,7, Ying-Chu Lin8, Chung-Ho Chen8, Suh-Hang Hank Juo9,10
1Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
2Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
3Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan
4Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
6Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
8School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
9Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
10Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Correspondence to:
Suh-Hang Hank Juo, e-mail: [email protected]
Keywords: microRNA-210, SPRED2, oxLDL, DNA methylation, atherosclerosis
Received: January 28, 2015 Accepted: May 21, 2015 Published: June 03, 2015
ABSTRACT
Hyperlipidemia, including the oxidized low-density lipoprotein (oxLDL) accumulation, is a risk and highly associated with the development of cancers and cardiovascular diseases. microRNA-210 (miR-210), a hypoxia-responsive microRNA regulated by HIF-1α, has been implicated in cancer and cardiovascular disease formation. Furthermore, Bioinformatics analysis revealed that the promoter of the miR-210 gene contains CpG-rich regions. It is unclear whether miR-210 expression could be epigenetically regulated in these disease progresses. The study aimed to explore the relationships between lipid and miR-210 in the context of cardiovascular disease and gastrointestinal cancer. We demonstrated oxLDL can decrease methylation in the miR-210 promoter to up-regulate miR-210. HIF-1α can bind to miR-210 promoter, but this HIF-1α binding site can be blocked by methylation. We showed that subjects of carotid atherosclerosis, stroke patients and cancer patients had hypomethylation in the miR-210 promoter, especially the HIF-1α binding site. Furthermore, miR-210 can directly inhibit sprouty-related EVH1 domain 2 (SPRED2) expressions, and SPRED2 reduces cell migration via ERK/c-Fos/MMPs pathways. Increased miR-210 and reduced SPRED2 levels were found in aorta of mice under high-fat diet and tumor tissues, which implied that miR-210 can be an underlying mechanism to explain oxLDL as a common risk factor for cardiovascular disease and gastrointestinal cancer.
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