Association between lipid peroxidation biomarkers and microRNA expression profiles
Yingya Zhao,
Marina S. Nogueira,
Ginger L. Milne,
Xingyi Guo,
Hui Cai,
Qing Lan,
Nathaniel Rothman,
Qiuyin Cai,
Yu-Tang Gao,
Qingxia Chen,
Xiao-Ou Shu,
Gong Yang
Affiliations
Yingya Zhao
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Marina S. Nogueira
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Ginger L. Milne
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Xingyi Guo
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Hui Cai
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Qing Lan
Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA
Nathaniel Rothman
Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA
Qiuyin Cai
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Yu-Tang Gao
Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Qingxia Chen
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
Xiao-Ou Shu
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Gong Yang
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author. 2525 West End Avenue, Suite 600, Nashville, TN, 37203, USA.
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 F2-isoprostanes (F2-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-F2t-IsoP (F2-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 F2-IsoPs and F2-IsoP-M, respectively. When further controlling for multiple comparisons, none of these nominally significant associations with F2-IsoPs was retained, whereas 71 of 213 miRNAs associated with F2-IsoP-M remained. The predicted targets of the F2-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.
