Silencing Aurora-A with siRNA inhibits cell proliferation in human lung adenocarcinoma cells

Int J Oncol. 2016 Sep;49(3):1028-38. doi: 10.3892/ijo.2016.3605. Epub 2016 Jul 5.

Abstract

Aurora kinase A (AURKA) is an oncogenic serine/threonine kinase, it plays important roles in tumorigenesis and chemoresistance. In this study, we investigated the expression of AURKA in lung adenocarcinoma tissues, the role of small interference RNA targeting AURKA on growth, cell cycle, and apoptosis of lung adenocarcinoma cell lines in vitro. The AURKA is highly expressed in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down AURKA expression in human lung adenocarcinoma cell lines H1299 and A549. The results indicated that depletion of AURKA could inhibit cell growth, cause cell cycle arrest and apoptosis. The potential mechanisms of AURKA inhibition induced cell cycle arrest and apoptosis are associated with downregulated RAF-1, CCND2, CCND3, CDK4, PAK4, EGFR and upregulated WEE1 expression. Furthermore, AURKA knockdown cooperated with vincristine (VCR) to repress A549 cell proliferation. Therefore, AURKA plays important roles in the proliferation of human lung adenocarcinoma cells, which suggests that AURKA could be a promising tool for lung adenocarcinoma therapy.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged, 80 and over
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / genetics*
  • Aurora Kinase A / metabolism*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Synergism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Lentivirus / genetics
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Prognosis
  • RNA, Small Interfering / pharmacology*
  • Vincristine / pharmacology*

Substances

  • RNA, Small Interfering
  • Vincristine
  • AURKA protein, human
  • Aurora Kinase A