DNM3 Attenuates Hepatocellular Carcinoma Growth by Activating P53

Med Sci Monit. 2016 Jan 19:22:197-205. doi: 10.12659/msm.896545.

Abstract

Background: Primary hepatocellular carcinoma is one of the most common malignant tumors in China and its mortality rate shows no sign at present of ceasing to rise. In our previous study, we found that the mRNA level of Dynamin3 (DNM3), a member of the Dynamin family, is significantly lower in hepatocellular carcinoma tissues than in non-tumor tissues. The aim of this study was to investigate the expression pattern and potential function of DNM3 in hepatocellular carcinoma.

Material/methods: First, we determined the expression ofDNM3 in human hepatocellular carcinoma tissues and cell lines. We then studied the biological function of DNM3 on hepatocellular carcinoma cells by proliferation assay and colony formation assay. Flow cytometry was used to study the effect of DNM3 on cell cycle and apoptosis.

Results: Expression of DNM3 was significantly downregulated in hepatocellular carcinoma tissues and was associated with vein invasion and tumor metastasis. In addition, upregulation of DNM3 reduced hepatocellular carcinoma cell proliferation and colony formation, induced hepatocellular carcinoma cell G0/G1 phase arrest, and stimulated hepatocellular carcinoma cell apoptosis. We also found that DNM3 may exert its anti-proliferative effect through upregulating p53.

Conclusions: Our findings suggest that DNM3 attenuates the proliferation and induces apoptosis of gastric cancer cells. Modulation of DNM3 may prove to be an efficient method of hepatocellular carcinoma treatment.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Dynamin III / genetics
  • Dynamin III / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / genetics

Substances

  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Dynamin III