Research Paper|Volume 12, Issue 9|pp 8352—8371

Exosomal miR-183-5p promotes angiogenesis in colorectal cancer by regulation of FOXO1

Anquan Shang¹, Xuan Wang², Chenzheng Gu¹, Wenfang Liu³, Junjun Sun¹, Bingjie Zeng¹, Chen Chen¹, Ping Ji¹, Junlu Wu¹, Wenqiang Quan¹, Yiwen Yao⁴, Weiwei Wang⁵, Zujun Sun¹, Dong Li¹

¹Department of Laboratory Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, P.R. China
²Department of Pharmacy, Putuo People’s Hospital, Shanghai, P.R. China
³Department of General Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, P.R. China
⁴Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
⁵Department of Pathology, The Sixth People's Hospital of Yancheng, Yancheng, P.R. China

* Equal contribution

Received: January 28, 2020Accepted: March 31, 2020Published: May 3, 2020

https://doi.org/10.18632/aging.103145

Copyright © 2020 Shang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in exosomes secreted from the CRC cells were investigated. Initially, microarray analysis was employed to determine the differentially expressed miRNAs. Exosomes isolated from CRC cells were co-cultured with HMEC-1 cells to explore the role of exosomes in angiogenesis. Further, the effects of CRC cell-derived exosomal miR-183-5p on proliferation, invasion and tube formation abilities of HMEC-1 cells were assessed. The preventative effect of exosomal miR-183-5p in vivo was measured in nude mice. Initially, it was found that FOXO1 was downregulated while miR-183-5p was upregulated in CRC. Additionally, the inhibition of miR-183-5p was suggested to suppress proliferation, invasion and tube formation abilities of HMEC-1 cells through upregulating FOXO1. Then, in vitro assays demonstrated that CRC cell-derived exosomes overexpressing miR-183-5p contributed to an enhanced proliferation, invasion and tube formation abilities of HMEC-1 cells. Furthermore, in vivo experiments confirmed the tumor-promotive effects of CRC cell-derived exosomal miR-183-5p. Collectively, our study demonstrates that the CRC cell-derived exosomes overexpressing miR-183-5p aggravates CRC through the regulation of FOXO1. Exosomes overexpressing miR-183-5p might be a potential treatment biomarker for CRC.