Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis

Abstract

Adipose tissue has long been considered to be involved in tumor progression. However, the adipocyte-secreted molecular determinants that regulate hepatocellular cancer progression have not been defined yet. In this study, the expression pattern of exosome miRNAs in hepatocellular carcinoma (HCC) patients with high body fat ratio (BFR) were identified by using low-density microarray. And the targets of exosome-miRNAs in HCC cells were predicted by bioinformatics methods and verified by in vitro as well as in vivo experiments. Here, we show that microRNA-23a/b (miR-23a/b) was significantly upregulated in both serum exosomes and tumor tissues of HCC patients with a high body fat ratio than low BFR. Subsequently, in vitro studies suggested that miR-23a/b was most likely to be derived from adipocytes and was transported into cancer cells via exosomes, thus promoting HCC cell growth and migration. Meanwhile, exosome miR-23a and miR-23b confer chemoresistance by targeting the von Hippel-Lindau/hypoxia-inducible factor axis. Our study provides evidence in that high BFR-related exosome miR23-a/b is a promising target for future treatment of HCC.