PLEK2 promotes the proliferation and migration of non-small cell lung cancer cells in a BRD4-dependent manner

Mol Biol Rep. 2022 May;49(5):3693-3704. doi: 10.1007/s11033-022-07209-3. Epub 2022 Feb 5.

Abstract

Background: It has been reported that Pleckstrin 2 (PLEK2) acts as an oncogene in non-small cell lung cancer (NSCLC). Bromodomain containing protein 4 (BRD4), an important transcriptional regulator of tumorigenesis, has been shown to play a key role in NSCLC. However, whether BRD4 regulates the transcription of PLEK2 and further promotes the proliferation and migration of NSCLC remains unknown.

Methods and results: In this study, we performed western blotting, real-time quantitative polymerase chain reaction, immunofluorescence, cell scratch wound assay and chromatin immunoprecipitation. According to these results, we found that PLEK2 plays a tumor‑promoting role in NSCLC via the PI3K/AKT signaling pathway. Moreover, BRD4 expression is significantly upregulated in NSCLC cell lines and suppression of BRD4 expression by siBRD4 and JQ-1 inhibits NSCLC cell lines proliferation and migration. Prominently, we first confirmed that BRD4 binds to the promoter region of the PLEK2 gene, which explains the mechanism by which BRD4 regulates the transcription of PLEK2 gene from the perspective of epigenetics.

Conclusions: The present study suggested that PLEK2 promotes the proliferation and migration of NSCLC in a BRD4-dependent manner and provided key insights into the potential avenues for preventing and treating NSCLC.

Keywords: BRD4; Migration; NSCLC; PLEK2; Proliferation.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • PLEK2 protein, human
  • Transcription Factors