Bone marrow mesenchymal stem cell-derived exosomal MiR-338-3p represses progression of hepatocellular carcinoma by targeting ETS1.

ABSTRACT

The present study aims to explore the function of human bone marrow mesenchymal stem cell (BMSC)-derived exosomal micro ribonucleic acid (miR)-338-3p in hepatocellular carcinoma (HCC) and further investigate its effect on HCC cell functions. Firstly, BMSCs were co-cultured with HCC cells, and BMSC-derived exosomes were identified. Next, Transwell assay and methyl thiazolyl tetrazolium (MTT) experiments were carried out to detect the effects of miR-338-3p and E26 transformation specific-1 (ETS1) on the viability, invasion, migration, and apoptosis of HCC cells through the exosomes derived from BMSCs. Furthermore, the targeting relationship between miR-338-3p and EST1 was verified via bioinformatics study and dual-luciferase reporter gene analysis. Additionally, Western blotting (WB) was carried out to measure the expression levels of EST1 and other proteins in HCC cells. It was found that BMSCs inhibited HCC cell proliferation, invasion and migration, and induced cell apoptosis, while the inhibitors of exosomes played the opposite roles. In addition, the up-regulation of exosomal miR-338-3p or the silencing of EST1 restrained HCC cell proliferation, invasion and migration, and induced cell apoptosis. In conclusion, BMSC-derived exosomal miR-338-3p delays the development of HCC by down-regulating EST1, providing a new promising treatment target for HCC.