ShRNA-mediated silencing of the Ndc80 gene suppress cell proliferation and affected hepatitis B virus-related hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2016 Jun;40(3):297-303. doi: 10.1016/j.clinre.2015.08.002. Epub 2015 Sep 14.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies in the world, and hepatitis B virus (HBV) has been well established to cause HCC. Ndc80 complex is a conserved mitotic regulator dedicated to ensuring faithful chromosome segregation and plays an important role in inducing tumor formation. However, its role in HCC caused by HBV infection remains unclear.

Methods: Immunohistochemistry (IHC), Western blot (WB), and real-time qRT-PCR were used to measure the expression of Ndc80 in HBV-related HCC tissues. Ndc80-specific short hairpin RNA (shRNA) was used to knock-down Ndc80 expression in the hepatoma cell line HeG2 and HepG2.2.15, which is stable transcribed with HBV genome. Furthermore, the effect of Ndc80 on cellular proliferation and growth were examined, respectively.

Results: The expression level of Ndc80 was remarkably up-regulated in HBV-related HCC tissues. Down-regulation of Ndc80 expression suppressed HBV replication. With cell counting and the MTS assay, cellular proliferation and growth of Ndc80 knocking-down cell line was shown to be effectively restrained.

Conclusion: This study suggests that Ndc80 may play an important role in the process of HBV-related HCC, and that it may be a potential biological treatment target in the future.

MeSH terms

  • Carcinoma, Hepatocellular / virology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins
  • Down-Regulation
  • Gene Silencing*
  • Hepatitis B virus / pathogenicity*
  • Humans
  • Liver Neoplasms / virology*
  • Nuclear Proteins / genetics*
  • RNA, Small Interfering*
  • Up-Regulation
  • Virus Replication / genetics

Substances

  • Cytoskeletal Proteins
  • NDC80 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering