ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2

Biochem Biophys Res Commun. 2019 Aug 13;516(1):278-284. doi: 10.1016/j.bbrc.2019.06.115. Epub 2019 Jun 25.

Abstract

The oncogenic roles of ETV4 have been revealed in multiple cancers. However, its expression and functions in lung cancer are rarely explored. Here, we firstly detected the expression of ETV4 in lung adenocarcinoma (LUAD) via online data and local experiment validation. Furthermore, we explored the functions and corresponding mechanisms of ETV4 in LUAD. Upregulation of ETV4 in LUAD is indicated by online data and our results of qPCR, Western blot and immunohistochemistry in collective tissue samples. ETV4 knockdown significantly inhibits proliferation and invasion in LUAD indicated by the outcomes of CCK8, plate clone formation, and Transwell invasion assays. Mechanistically, chromatin immunoprecipitation and luciferase reporter system assays indicated that ETV4 could directly bind at the promoter of MSI2 and promote its transcription. Furthermore, ectopic expression MSI2 can rescue the inhibitory effects caused by ETV4 knockdown in LUAD. Therefore, we proved that upregulation of ETV4 could promote proliferation and invasion of LUAD by transcriptionally upregulating MSI2 offering a potential therapy treatment target of LUAD.

Keywords: ETV4; Lung adenocarcinoma; MSI2; Proliferation and invasion; Transcription regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Proto-Oncogene Proteins c-ets / genetics*
  • RNA-Binding Proteins / genetics*
  • Transcriptional Activation
  • Up-Regulation

Substances

  • ETV4 protein, human
  • MSI2 protein, human
  • Proto-Oncogene Proteins c-ets
  • RNA-Binding Proteins