Knockdown of CPEB4 expression suppresses cell migration and invasion via Akt pathway in non-small cell lung cancer

Cell Biol Int. 2018 Nov;42(11):1484-1491. doi: 10.1002/cbin.10930. Epub 2018 Feb 1.

Abstract

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) could be an important regulator in variety of cancers. However, the biological function and the underlying molecular mechanism of CPEB4 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the metastasis role of CPEB4 in NSCLC cells, we knocked down CPEB4 using siRNA. Transwell migration assay and cell invasion assay on Matrigel were presented, and cell migration was also determined by scratch-healing assay. ROS generation were determined by fluorescence probe DCFH2-DA. The protein expression was assessed by ELISA and Western blot analysis. LY294002 were used to inhibit PI3 K/Akt signaling. The data showed that knockdown of CPEB4 inhibited the migration and invasion of NSCLC. Moreover, silencing of CPEB4 reduced Snail and MMP-3 expression in vitro. We also indicated that CPEB4 knockdown increased the ROS expression. Furthermore, we found that silencing of CPEB4 decreased pAkt expression. Taken all together, our data demonstrated that silencing of CPEB4 induces ROS generation, thus suppressing the Akt expression, which finally prevents NSCLC cells invasion and migration. Therefore, CPEB4 may regard as a target to inhibit NSCLC invasion and metastasis through Akt pathway.

Keywords: CPEB4; invasion; migration; non-small cell lung cancer.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Chromones / pharmacology
  • Gene Knockdown Techniques*
  • Gene Silencing / drug effects
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Matrix Metalloproteinase 3 / metabolism
  • Morpholines / pharmacology
  • Neoplasm Invasiveness
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Snail Family Transcription Factors / metabolism

Substances

  • CPEB4 protein, human
  • Chromones
  • Morpholines
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • Snail Family Transcription Factors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • MMP3 protein, human
  • Matrix Metalloproteinase 3