Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210

Ku Chung Chen, Yi Chu Liao, Jaw Yuan Wang, Ying Chu Lin, Chung Ho Chen, Suh Hang Hank Juo

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)24105-24118
Number of pages14
JournalOncotarget
Volume6
Issue number27
DOIs
Publication statusPublished - 2015

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Keywords

  • Atherosclerosis
  • DNA methylation
  • microRNA-210
  • OxLDL
  • SPRED2

ASJC Scopus subject areas

  • Oncology

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