8-Oxoguanine modifications in peripheral leukocyte microRNAs promote age-related inflammation by remodeling gene regulatory networks.

Ming-Ming Han, Qian Liu, Lan Yang, Jin Li, Qing-Yu Wang, Ying-Min Zhang, Jia-Qi Guo, Lv-Tao Zeng, Ruo-Mei Qi, Jian-Ping Cai

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China; Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China; Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. · pubmed

Paper

Abstract

The role of reactive oxygen species (ROS) in cellular senescence and inflammation has been extensively studied; however, the specific molecular mechanisms underlying these effects have yet to be fully elucidated. By applying a nucleotide pool detection system, oxidative microRNA sequencing, and cytokine chip detection techniques, we found that the levels of 8-oxo-guanosine triphosphate (8-oxo-GTP) increased with age and were positively correlated with elevated levels of oxidized microRNA and increased levels of inflammatory factors. During aging, guanine residues in the seed regions of miR-98-5p that regulates ICAM1, and miR-8085 that regulates CXCL16, were oxidized to 8-oxoguanine. This oxidation weakened the binding affinity of microRNAs to their target genes, thereby promoting the expression of ICAM1 and CXCL16. Oxidized microRNAs can regulate new target genes via o

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Research summary

The paper claims that oxidative modifications of microRNAs contribute to age-related inflammation by altering gene regulatory networks. This research is relevant as it explores the molecular mechanisms of aging and inflammation, potentially addressing root causes of age-related diseases.

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