Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma

• Published in: Frontiers in cell and developmental biology 2021-03, Vol.9, p.633358
• Main Authors: Dong, Shuang-Shuang, Dong, Dan-Dan, Yang, Zhang-Fu, Zhu, Gui-Qi, Gao, Dong-Mei, Chen, Jie, Zhao, Yan, Liu, Bin-Bin
• Format: Article
• Language: English
• Subjects: angiogenesis; ANGPT1; Cell and Developmental Biology; exosomes; HCC; miR-3682-3p
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.633358

Angiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated. Exosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively. and analyses showed that exosomes isolated from highly metastatic HCC cells enhanced the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) compared to exosomes derived from poorly metastatic HCC cells. In addition, microarray analysis of HCC-Exos was conducted to identify potential functional molecules, and miR-3682-3p expression was found to be significantly downregulated in exosomes isolated from highly metastatic HCC cells. By gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis. Our study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.