Research Paper Volume 12, Issue 9 pp 8549—8564
Exosomal miRNA-34 from cancer-associated fibroblasts inhibits growth and invasion of gastric cancer cells in vitro and in vivo
- 1 Endoscope Room, Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
- 2 Medical College of Hebei University, Shijiazhuang 050011, Hebei Province, China
- 3 The First Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
- 4 Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050020, Hebei Province, China
- 5 Department of Neurosurgery, Affiliated hospital of Hebei university, Baoding 071000, Hebei Province, China
- 6 Hebei University, Baoding 071002, Hebei Province, China
Received: January 8, 2020 Accepted: March 4, 2020 Published: May 10, 2020https://doi.org/10.18632/aging.103157
How to Cite
Copyright © 2020 Shi 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.
Gastric cancer (GC) is one of the most common malignancies worldwide manifesting high morbidity and mortality. Cancer-associated fibroblasts (CAFs), important components of the tumor microenvironment, are essential for tumorigenesis and progression. Exosomes secreted from CAFs have been reported as the critical molecule-vehicle in intercellular crosstalk. However, the precise mechanism underlying the effect of CAFs remains to be fully investigated. In this study, we aimed to determine the role of CAFs and their exosomes in the progression of GC and related mechanisms. The results revealed that miRNA-34 was downregulated in both GC fibroblasts (GCFs) and GC cell lines while the overexpression of miRNA-34 suppressed the proliferation, invasion, and motility of GC cell lines. Coculturing GC cells with miRNA-34-overexpressing GCFs led to the suppression of cancer progression. Also, exosomes derived from GCFs were taken up by GC cells in vitro and in vivo and exerted antitumor roles in GC. In addition, exosomal miRNA-34 inhibited GC cell proliferation and invasion in vitro and suppressed tumor growth in vivo. Furthermore, 16 genes were identified as potential downstream targeting genes of miRNA-34. Taken together, GCFs-derived exosomal miRNA-34 may be a promising targeting molecule for therapeutic strategies in GC.