Gastric cancer–secreted exosomal X26nt increases angiogenesis and vascular permeability by targeting VE‐cadherin

Abstract

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.

RETRACTED ARTICLE: microRNA-10a-5p from gastric cancer cell-derived exosomes enhances viability and migration of human umbilical vein endothelial cells by targeting zinc finger MYND-type containing 11

“…has depicted a pro-tumor role of GC cells-released exo, which could augment expansion of myeloid-derived suppressor cells through a transfer of miR-107 [ 34 ]. GC cells-derived exo activates HUVECs to proliferate, migrate and form tubes, and such effects are enhanced via transfer of 26-nt-long ncRNA [ 35 ].…”

Exosomal lncRNA ATB Derived from Ovarian Cancer Cells Promotes Angiogenesis via Regulating miR-204-3p/TGFβR2 Axis

“…Additionally, it has been reported that exosomes secreted from cancer cells could be transported to HUVECs. 19 Therefore, we next investigate whether exosomes secreted from ovarian cancer cells could be transported to HUVECs. As showed in Figure 2D and E , PKH26 labeled exosomes were absorbed by HUVECs in a time dependent manner, and these phenomena were notably reversed in the presence of nystatin or heparin.…”

The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer

“…Vascular endothelial cadherin (VE-cadherin) has been shown to enhance vascular permeability, angiogenesis and tumor growth ( Viallard and Larrivée, 2017 ). The exosomal 26‐nt‐long ncRNA (X26 nt) secreted by GCs can target VE-cadherin to increase angiogenesis and vascular permeability ( Chen et al, 2021a ). The long-chain non-coding RNA MALAT1 was shown to enhance the expression of classic markers such as VE-cadherin and components of related signaling pathways to promote blood vessel growth and angiogenesis ( Li et al, 2017a ).…”