Hypoxia LUAD H1975 cell-derived exosomal miR-671-3p promotes angiogenesis via regulating KLF2-VEGFR2 axis

被引:0
作者
Kun Liu [1 ]
Yi Wang [2 ]
Qisen Li [1 ]
Yujue Wang [1 ]
Jinrui Liu [1 ]
Jintao Zhou [1 ]
Feiyu Song [3 ]
Zhongyi Cong [4 ]
Zhe Wang [1 ]
Ning Kong [2 ]
机构
[1] Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, ChangChun
[2] Beijing University of Chinese Medicine, Beijing
[3] Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun
[4] Jilin Connell Pharmaceutical Company, Changchun
基金
中国博士后科学基金;
关键词
Angiogenesis; Exosome; Hypoxia; LUAD; miR-671-3p; Premetastatic niche;
D O I
10.1038/s41598-025-97488-0
中图分类号
学科分类号
摘要
For solid tumors, hypoxia is associated with disease aggressiveness and poor outcomes. In addition to undergoing broad intracellular molecular and metabolic adaptations, hypoxic tumor cells extensively communicate with their microenvironments to facilitate conditions favorable for their survival, growth, and metastasis. This communication is mediated by diverse secretory factors, including exosomes (extracellular vesicles of endosomal origin). Exosomal cargo is altered considerably by hypoxia, with significant impacts on tumor-cell communication with both local and distant microenvironments. Exosomes released by cancer cells influence the tumor environment to accelerate metastasis. While tumor-derived exosomes have been identified as a major driver of premetastatic niche formation at distant sites, this mechanism in lung adenocarcinoma (LUAD) remains unclear. We found that miR-671-3p in exosomes derived from H1975 under hypoxic conditions target Krüppel-like factor 2 (KLF2) to regulate VEGFR2 expression in endothelial cells to promote angiogenesis. In addition, miR-671-3p is expressed at high levels in circulating exosomes isolated from patients with LUAD. Our study suggests that exosome miR-671-3p is involved in the formation of premetastatic niche and may serve as a blood-based biomarker for LUAD metastasis. © The Author(s) 2025.
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