ZNF185 inhibits growth and invasion of lung adenocarcinoma cells through inhibition of the akt/gsk3β pathway

J Biol Regul Homeost Agents. 2016 Jul-Sep;30(3):683-691.

Abstract

Zinc finger (ZNF) proteins, a diverse family of proteins, have multiple biological functions in cancer. Increased expression of ZNF185 has been involved in the regulation of tumor growth and metastasis. However, the function and underlying mechanisms of ZNF185 in the tumorigenesis of lung adenocarcinoma (LAC) remain unclear. The protein expression of ZNF185 was examined in human LAC tissues by immunohistochemical assay. After lentiviral vector-mediated ZNF185 overexpression was infected into the LAC cell lines (A549 and LETPα-2), cell growth and invasive potential were respectively evaluated by MTT and Transwell assays. We found that the protein expression of ZNF185 was significantly downregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (37.10% vs 58.06%, P=0.015), and was negatively correlated with the lymph node metastasis of the LAC patients (P=0.005). Furthermore, overexpression of ZNF185 reduced cell proliferation and invasion in LAC cells, followed by the downregulation of p-AKT, p-GSK3β, VEGF and MMP-9 expression. Taken together, our findings indicate that the decreased expression of ZNF185 is linked to the tumor metastasis in human LAC patients, and ZNF185 overexpression inhibits the growth and invasion of LAC cells through inhibition of the AKT/GSK3β signaling, suggesting that ZNF185 may represent a potential therapeutic target for the treatment of LAC.

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / biosynthesis
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / physiology
  • Humans
  • LIM Domain Proteins / biosynthesis
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / physiology*
  • Lung Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / drug effects*
  • Tumor Burden

Substances

  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • Neoplasm Proteins
  • ZNF185 protein, human
  • AKT1 protein, human
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • MMP9 protein, human
  • Matrix Metalloproteinase 9