Exosome-transmitted circular RNA hsa_circ_0051443 suppresses hepatocellular carcinoma progression

Cancer Lett. 2020 Apr 10:475:119-128. doi: 10.1016/j.canlet.2020.01.022. Epub 2020 Jan 31.

Abstract

Extracellular communication in the tumor microenvironment is critical. Results of qRT-PCR show that circ-0051443 is significantly lower in the plasma exosomes and tissues from patients with hepatocellular carcinoma (HCC) than healthy controls. Compared with the producer cells, circ-0051443 is mainly packaged into exosomes. A receiver operating characteristic curve (ROC) shows that the patients with HCC can be distinguished from the controls by exosomal circ-0051443. The role of exosomal circ-0051443 in HCC was determined by animal and cell analyses. Circ-0051443 is transmitted from normal cells to HCC cells via exosomes and suppresses the malignant biological behaviors by promoting cell apoptosis and arresting the cell cycle. Exosomal circ-0051443 decreases the weight and volume of the xenograft tumors in nude mice via BAK1 upregulation in these tumors. BAK1 expression is mediated by exosomal circ-0051443 through competitive bound to miR-331-3p. Therefore, exosomal circ-0051443 can serve as a predictor and potential therapeutic target for HCC.

Keywords: Biomarker; Extracellular vesicles; Liver cancer; circRNA; miRNA.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation
  • Exosomes / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Prognosis
  • RNA, Circular / genetics*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*

Substances

  • BAK1 protein, human
  • Biomarkers, Tumor
  • MIRN331 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • bcl-2 Homologous Antagonist-Killer Protein