Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1
Open Access
- 4 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (6), 1-14
- https://doi.org/10.1038/s41419-021-03803-8
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.Keywords
Funding Information
- National Natural Science Foundation of China (81702399, 81472275)
- Natural Science Foundation of Guangdong Province (2017A030313618, 2020A151501303)
This publication has 45 references indexed in Scilit:
- The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancerGynecologic Oncology, 2014
- miR-21 coordinates tumor growth and modulates KRIT1 levelsBiochemical and Biophysical Research Communications, 2013
- Vascular Permeability and Drug Delivery in CancersFrontiers in Oncology, 2013
- Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polypsGut, 2011
- MiR-21 Induced Angiogenesis through AKT and ERK Activation and HIF-1α ExpressionPLOS ONE, 2011
- Rap1 and its effector KRIT1/CCM1 regulate β-catenin signalingDisease Models & Mechanisms, 2010
- Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer DevelopmentClinical Cancer Research, 2009
- MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancerOncogene, 2007
- Role of angiogenesis in tumor growth and metastasisSeminars in Oncology, 2002
- Signaling through ?-catenin and Lef/TcfCellular and Molecular Life Sciences, 1999