Hypoxic BMSC-derived exosomal miR-652-3p promotes proliferation and metastasis of hepatocarcinoma cancer cells via targeting TNRC6A

Aging (Albany NY). 2023 Nov 16;15(22):12780-12793. doi: 10.18632/aging.205025. Epub 2023 Nov 16.

Abstract

Cancer microenvironment plays an important role in the proliferation and metastasis of hepatocarcinoma cancer cells (HCC). Exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment. In this study, we reveal that miRNA-652-3P from BMSC-derived exosomes promotes proliferation and metastasis in HCC. The ability of cancer proliferation, migration and invasion can be evaluated after co-culture by CCK-8, wound healing and transwell assay. Isolated exosomes were identified by transmission electron microscopy (TEM) and the biomarkers of the purified exosomes were showed in West-blotting (WB). MiR-652-3p was detected in the HepG2 and 7721 after co-culturing with exosome derived from BMSCs under different conditions. Target authentication was performed by a luciferase reporter assay to confirm the presumptive target of miR-652-3p. After overexpressing miR-652-3p, the mRNA and protein expression level of TNRC6A in HCC was examined by q-PCR and WB. Further, we observed greater miR-652-3p upregulation in hypoxic BMSCs-exosomes than in normal- exosomes. In addition, a miR-652-3p inhibitor attenuates the proliferation and metastasis of HCC cells after co-culturing with BMSCs. Our data demonstrate that hypoxic BMSCs-derived exosomal miR-652-3p promotes proliferation in HCC cells by inhibiting TNRC6A. The BMSCs-derived exosomal miR-652-3p may help find patient-targeted therapies in hepatocarcinoma cancer.

Keywords: TNRC6A; exosome; hypoxic BMSCs; miR-652-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Cell Proliferation / genetics
  • Humans
  • Hypoxia
  • Liver Neoplasms* / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Tumor Microenvironment / genetics

Substances

  • MicroRNAs
  • MIRN652 microRNA, human
  • TNRC6A protein, human