title: Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210.
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.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ku-Chung
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Lin
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001665:Binding Sites; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism; D002465:Cell Movement; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000860:Hypoxia; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D000097584:DNA Methyltransferase 3B; C543800:MIRN210 microRNA, human; C549325:MIRN210 microRNA, mouse; C099252:oxidized low density lipoprotein
keywords: DNA methylation; SPRED2; atherosclerosis; microRNA-210; oxLDL