Open AccessGastric cancer–secreted exosomal X26nt increases angiogenesis and vascular permeability by targeting VE‐cadherin
Author(s) -
Chen Xiaocui,
Zhang Shuqiong,
Du Kun,
Zheng Naisheng,
Liu Yi,
Chen Hui,
Xie Guohua,
Ma Yanhui,
Zhou Yunlan,
Zheng Yingxia,
Zeng Lingfang,
Yang Junyao,
Shen Lisong
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14740
Subject(s) - angiogenesis , microvesicles , umbilical vein , biology , cancer research , metastasis , ve cadherin , microbiology and biotechnology , tumor progression , cancer , microrna , cadherin , cell , biochemistry , genetics , in vitro , gene
Angiogenesis is closely associated with tumorigenesis, invasion, and metastasis by providing oxygen and nutrients. Recently, increasing evidence indicates that cancer‐derived exosomes which contain proteins, coding, and noncoding RNAs (ncRNAs) were shown to have proangiogenic function in cancer. A 26‐nt‐long ncRNA (X26nt) is generated in the process of inositol‐requiring enzyme 1 alpha (IRE1α)‐induced unspliced XBP1 splicing. However, the role of X26nt in the angiogenesis of gastric cancer (GC) remains largely unknown. In the present study, we found that X26nt was significantly elevated in GC and GC exosomes. Then, we verified that X26nt could be delivered into human umbilical vein endothelial cells (HUVECs) via GC cell exosomes and promote the proliferation, migration, and tube formation of HUVECs. We revealed that exosomal X26nt decreased vascular endothelial cadherin (VE‐cadherin) by directly combining the 3′UTR of VE‐cadherin mRNA in HUVECs, thereby increasing vascular permeability. We further demonstrated that X26nt accelerates the tumor growth and angiogenesis in a mouse subcutaneous tumor model. Our findings investigate a unique intercellular communication mediated by cancer‐derived exosomes and reveal a novel mechanism of exosomal X26nt in the regulation of tumor vasculature.