Cancer-Associated Fibroblast-Secreted Exosomes Promote Malignant Advancement of Liver Cancer by Regulating the miR-208a-5p/ESR1 Axis

Abstract

The malignant development of hepatic carcinoma is accelerated by cancer-associated fibroblasts (CAFs) and contributes to its high mortality rate. CAF-derived exosomes are involved in liver cancer progression. We evaluated the role of exosomes from CAFs in liver cancer. Exosomes were collected from CAFs isolated from tumor tissues. Cellular processes were determined through cell counting kit-8, colony formation, as well as Transwell assay. miR-208a-5p and ESR1 expression was examined using quantitative real-time PCR, and their interaction was confirmed using luciferase reporter analysis. Exosomes were successfully isolated from CAFs. CAF-secreted exosomes promoted the viability, colonies, migration, as well as invasion of tumor cells. miR-208a-5p was upregulated after treatment with exosomes. Downregulation of miR-208a-5p inhibited biological behaviors by targeting ESR1. Additionally, downregulating miR-208a-5p abrogated the cell phenotypes changed by exosomes. In conclusion, CAFs promoted liver cancer progression, which was associated with the upregulation of miR-208a-5p by targeting ESR1. These findings suggested that targeting CAF-derived exosomes may contribute to liver cancer therapy.