Gold nano-particles (AuNPs) carrying miR-326 targets PDK1/AKT/c-myc axis in hepatocellular carcinoma

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2830-2837. doi: 10.1080/21691401.2018.1489266.

Abstract

Abnormal expression of microRNAs (miRNAs) contributes to tumour growth and invasion. MiR-326 expression often down-regulates in several kinds of cancer and low expression of miR-326 is linked with poor prognosis in cancer patients. In the present study, we aimed to explore the modulatory mechanism of miR-326 in hepatocellular carcinoma (HCC). miR-326 expression was significantly decreased in HCC cell lines and tissues. miR-326 decreased HCC cell growth by affecting cell-cycle progression and by promoting apoptosis. In addition, miR-326 inhibited HCC cell invasion by decreasing the EMT phenotype. We found that miR-326 functioned as a tumour suppressor by repressing its down-stream target PDK1. C-myc contributed to miR-326 down-regulation through binding at its promoter and inhibited its expression. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying miR-326. Restoration of miR-326 reduced tumour growth in vivo. Our findings suggest that miR-326 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.

Keywords: PDK1; gold nano-particles; hepatocellular carcinoma; miR-326.

MeSH terms

  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Drug Carriers / chemistry
  • Epithelial-Mesenchymal Transition / genetics
  • Gold / chemistry*
  • Humans
  • Liver Neoplasms / pathology
  • Metal Nanoparticles / chemistry*
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Molecular Targeted Therapy
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase / metabolism*

Substances

  • Drug Carriers
  • MYC protein, human
  • MicroRNAs
  • PDK1 protein, human
  • Proto-Oncogene Proteins c-myc
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Gold
  • Proto-Oncogene Proteins c-akt