Zinc finger protein ZBTB20 promotes cell proliferation in non-small cell lung cancer through repression of FoxO1

FEBS Lett. 2014 Dec 20;588(24):4536-42. doi: 10.1016/j.febslet.2014.10.005. Epub 2014 Oct 13.

Abstract

In the present study, we found that ZBTB20, a member of the POK (POZ and Krüppel) family of transcriptional repressors, was significantly up-regulated in lung cancer tissues, compared with adjacent normal tissues. Our in vitro studies further found that ZBTB20 overexpression promoted, while its inhibition using small interfering RNA suppressed cell proliferation. Consistently, key regulators in cell-cycle progression, such as Cyclin D1, Cyclin E, P21 and P27, were also regulated by ZBTB20. At the molecular level, we further revealed that FoxO1, a tumor suppressor in multiple human cancers, was transcriptionally repressed by ZBTB20. Therefore, our results highlight an important role for ZBTB20 in controlling NSCLC development, which might be helpful to identify potential therapeutic targets for its treatment.

Keywords: Cell cycle; FoxO1; Non-small cell lung cancer; Zinc finger and BTB domain-containing 20.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Nerve Tissue Proteins
  • Transcription Factors
  • ZBTB20 protein, human