Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value

World J Gastroenterol. 2019 Apr 21;25(15):1890-1898. doi: 10.3748/wjg.v25.i15.1890.

Abstract

Background: Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC).

Aim: To understand the mechanism of exosomal microRNA-224 (miR-224) in the development of HCC and evaluate its diagnostic and prognostic value.

Methods: Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis.

Results: By targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.

Conclusion: Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.

Keywords: Biomarker; Exosome; Hepatocellular carcinoma; MicroRNA-224; Serum.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycine N-Methyltransferase / genetics*
  • Glycine N-Methyltransferase / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN224 microRNA, human
  • MicroRNAs
  • GNMT protein, human
  • Glycine N-Methyltransferase