Association between lipid peroxidation biomarkers and microRNA expression profiles

BACKGROUND: In-vitro and animal studies demonstrate that epigenetic regulation may play an important role in lipid peroxidation. No human study to date has directly evaluated microRNAs (miRNAs), as epigenetic modulators, in relation to systemic levels of lipid peroxidation. OBJECTIVES: To evaluate associations between systemic levels of lipid peroxidation and miRNA expression profiles in women. METHODS: Included in the analysis were 92 women aged 40–70 years, a subset of the Shanghai Women’s Health Study (SWHS). Lipid peroxidation was assessed by urinary markers F(2)-isoprostanes (F(2)-IsoPs), the products of free radical-catalyzed peroxidation of arachidonic acid, and its major metabolite after β-oxidation, 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (F(2)-IsoP-M), with GC/NICI-MS assays. Expression levels of 798 miRNAs were quantified in peripheral plasma with NanoString nCounter assays. A multivariable linear regression model was used to examine the association between lipid peroxidation and miRNA expression. RESULTS: After adjusting for potential confounders, 29 miRNAs and 213 miRNAs were associated with F(2)-IsoPs and F(2)-IsoP-M, respectively. When further controlling for multiple comparisons, none of these nominally significant associations with F(2)-IsoPs was retained, whereas 71 of 213 miRNAs associated with F(2)-IsoP-M remained. The predicted targets of the F(2)-IsoP-M associated miRNAs were enriched for several lipid peroxidation-related processes such as PI3K/AKT, MAPK, FOXO and HIF-1 signaling pathways. Moreover, 10 miRNAs (miR-93-5p, miR-761, miR-301b-3p, miR-497-5p, miR-141-3p, miR-186-5p, miR-126-3p, miR-200b-3p, miR-520d-3p, and miR-363-3p) exhibited functional interactions with 50 unique mRNAs targets involved in the regulation of β-oxidation. CONCLUSIONS: To our knowledge, this study, for the first time, provides human data suggesting that miRNA expression may be linked to lipid peroxidation products and their metabolism.