Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1

Abstract Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interactio...

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Main Authors: Qinglian He, Aihua Ye, Weibiao Ye, Xiaomin Liao, Guoqiang Qin, Yongqiang Xu, Yuting Yin, Huanqian Luo, Muhua Yi, Liying Xian, Shihao Zhang, Xiyuan Qin, Wei Zhu, Yuling Li
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-021-03803-8
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author Qinglian He
Aihua Ye
Weibiao Ye
Xiaomin Liao
Guoqiang Qin
Yongqiang Xu
Yuting Yin
Huanqian Luo
Muhua Yi
Liying Xian
Shihao Zhang
Xiyuan Qin
Wei Zhu
Yuling Li
author_facet Qinglian He
Aihua Ye
Weibiao Ye
Xiaomin Liao
Guoqiang Qin
Yongqiang Xu
Yuting Yin
Huanqian Luo
Muhua Yi
Liying Xian
Shihao Zhang
Xiyuan Qin
Wei Zhu
Yuling Li
author_sort Qinglian He
collection DOAJ
description Abstract Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.
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spelling doaj.art-2453b2bff10f447aa9beec21381307fb2022-12-21T19:18:45ZengNature Publishing GroupCell Death and Disease2041-48892021-06-0112611410.1038/s41419-021-03803-8Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1Qinglian He0Aihua Ye1Weibiao Ye2Xiaomin Liao3Guoqiang Qin4Yongqiang Xu5Yuting Yin6Huanqian Luo7Muhua Yi8Liying Xian9Shihao Zhang10Xiyuan Qin11Wei Zhu12Yuling Li13Department of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Obstetrics, Longhua District Maternity and Child Healthcare HospitalDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of science and education, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Guangdong Medical UniversityDepartment of Ultrasound, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityDepartment of Pathology, Guangdong Medical UniversityDepartment of Pathology, Dongguan People’s Hospital affiliated to Southern Medical UniversityAbstract Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.https://doi.org/10.1038/s41419-021-03803-8
spellingShingle Qinglian He
Aihua Ye
Weibiao Ye
Xiaomin Liao
Guoqiang Qin
Yongqiang Xu
Yuting Yin
Huanqian Luo
Muhua Yi
Liying Xian
Shihao Zhang
Xiyuan Qin
Wei Zhu
Yuling Li
Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
Cell Death and Disease
title Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
title_full Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
title_fullStr Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
title_full_unstemmed Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
title_short Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
title_sort cancer secreted exosomal mir 21 5p induces angiogenesis and vascular permeability by targeting krit1
url https://doi.org/10.1038/s41419-021-03803-8
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