MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance

Cancer Biomark. 2017;19(2):221-230. doi: 10.3233/CBM-170568.

Abstract

Backgrounds: Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and it is the most common primary malignant tumor of the liver. Till now the prognosis of HCC patients is generally poor. The molecular mechanism giving rise to HCC development and recurrence is still largely unknown. MicroRNA-31 (miR-31) is among the most commonly altered microRNAs in human cancers, and alternations of miR-31 expression were reported to play pivotal roles in tumorigenesis and tumor progression.

Methods: In this work, the primary biological function of miR-31 in HCC tumorigenesis was investigated.

Results: Our data showed that overexpression of miR-31 induced markedly inhibition of HCC cell proliferation, migration in vitro and inhibited xenograft tumor growth in vivo. One target gene of miR-31, NDRG3, was also demonstrated indispensable for HCC cell survival. Furthermore, miR-31 and NDRG3 were both essential for HCC cell drug resistance in adriamycin.

Conclusions: We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future.

Keywords: Hepatocellular carcinoma; NDRG3; adriamycin; miR-31; tumorigenesis.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / secondary*
  • Cell Movement
  • Cell Proliferation
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Prognosis
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN31 microRNA, human
  • MicroRNAs
  • NDRG3 protein, human
  • Nerve Tissue Proteins
  • Doxorubicin