Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis
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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.
KeywordsAdipose Exosomes miR-23 HIF HCC
This study was supported by the Hunan Natural Science Youth Fund Project (Project number: 2018JJ3784. Project name: Molecular mechanism of miR-1181 involvement in promoting proliferation and survival of hepatocellular)
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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