Exosomal MiRNAs as Predictive Biomarkers for Metabolic Syndrome: Insights into Biological Adaptation in a High Altitude Hypoxic Environment
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i3.4410
Abstract
This study integrates human cohorts (n=60, 30 high-altitude [4300m] vs. 30 low-altitude [50m]) and C57BL/6 mouse models to elucidate regulatory mechanisms of metabolic adaptation via serum exosomal miRNAs under hypoxic stress. High-altitude exposure significantly improved metabolic health in humans (reduced BMI, FBG, HOMA-IR, Tch, TG, LDL-C; increased HDL-C) and mice (decreased weight gain, insulin, FBG, HOMA-IR, FFA, TG; p<0.05). High-throughput sequencing identified 57 differentially expressed miRNAs (22↑/35↓) in hypoxic mice, enriched in Ras/MAPK signaling and metabolic networks. Cross-species validation confirmed hsa-miR-5100 (AUC=0.9089), hsa-miR-184-3p (AUC=0.8233), and hsa-miR-122-5p (AUC=0.7521) as diagnostic biomarkers. We propose the first "exosomal miRNA-signaling pathway-metabolic phenotype" trinity framework, providing novel targets for hypoxia adaptation and metabolic disease intervention.
Keywords
Exosomal miRNAs, High-altitude hypoxia, Metabolic adaptation, Hypoxic intervention biomarkers
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[8] Kumar A, Deep G (2020) Hypoxia in tumor microenvironment regulates exosome biogenesis: Molecular mechanisms and translational opportunities. Cancer Lett 479: 23–30.
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[13] Silina M, Dzhalilova D, Makarova O (2023) Role of microRNAs in regulation of cellular response to hypoxia. Biochemistry 88(6): 741–757.
[14] Colaianni F, Zelli V, Compagnoni C, Miscione M, Rossi M, et al. (2024) Role of circulating microRNAs in liver disease and HCC: Focus on miR-122. Genes 15(10): 1313.
[15] Zhang H, Li H, Wang G, Wang J, Xiang Y, et al. (2020) MKL1/miR-5100/CAAP1 loop regulates autophagy and apoptosis in gastric cancer cells. Neoplasia 22(5): 220–230.
[16] Bai Y, Chen K, Zhan J, Wu M (2020) miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis. Biosci Rep 40(6): BSR20191908.
[17] Li J, Zeng X, Wang W (2021) miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN. Exp Ther Med 22(5): 1278.
Copyright © 2025 Yifan Zhang, Yan Xu, Kang Song, Yuqin Zan, Jing Yang, Yujuan Qi, Qiang Zhang
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