期刊
CANCER SCIENCE
卷 112, 期 5, 页码 1839-1852出版社
WILEY
DOI: 10.1111/cas.14740
关键词
angiogenesis; exosomes; gastric cancer; noncoding RNAs; VE‐ cadherin
类别
资金
- National Natural Science Foundation of China [81802082, 81672363, 81873863]
- Shanghai Rising Stars of Medical Talent Youth Development Program-Clinical Laboratory Practitioners Program [2019016]
- Gao Yuan Development Program of Shanghai Municipal Education Commission
- Key Specialty Development Program of Shanghai Municipal Health Commission
This study found that X26nt is significantly elevated in gastric cancer and cancer cell exosomes, promoting the growth, migration, and tube formation of HUVECs. The research revealed how X26nt decreases VE-cadherin to increase vascular permeability and accelerates tumor growth and angiogenesis.
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 (IRE1 alpha)-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.
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