Hypoxic pancreatic cancer derived exosomal miR-30b-5p promotes tumor angiogenesis by inhibiting GJA1 expression

作者：Kai Chen, Qi Wang, Xinxin Liu, Feng Wang, Yinmo Yang, Xiaodong Tian · 发表于：International Journal of Biological Sciences · 年份：2022 · DOI：10.7150/ijbs.67675 · 被引用次数：134 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Cancer-related molecular mechanisms research

Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) have vascular invasion and metastasis, leading to low surgical resection rate and dismal prognosis. Tumor angiogenesis is related to vascular invasion and metastasis. However, anti-angiogenesis therapeutic effects in PDAC are limited. Therefore, it is imperative to explore molecular mechanism of angiogenesis in PDAC. Experimental Design: scRNA-seq data were utilized to delineatetranscriptional profiles of endothelial cells in PDAC. The in vitro and vivo angiogenesis models were used to explore the role of PDAC derived exosomes under hypoxic condition in tumor angiogenesis. Results: Endothelial cells in PDAC had distinct gene expression profiles compared with normal pancreas. The marker genes of endothelial cells in PDAC were enriched for hypoxia and angiogenesis. MiR-30b-5p were significantly enriched in hypoxic PDAC cells derived exosomes, which could be transferred to HUVEC, resulting in the upregulation of miR-30b-5p. Hypoxic PDAC cells derived exosomes could promote tube formation and endothelial cells migration via miR-30b-5p mediated downregulation of gap junction protein GJA1. Moreover, hypoxic PDAC cells derived exosomes increased new microvascular density in vivo. Patients with PDAC had higher levels of total miR-30b-5p and exosomal miR-30b-5p in peripheral blood plasma than healthy subjects. In addition, there were significant correlations for the levels of total miR-30b-5p or exosomal miR-30b-5p be...