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Transcriptional factor FOXO3 negatively regulates the expression of nm23-H1 in non-small cell lung cancer

Linlin Zhang1, Lin Li2, Huijun Wei2

  • 1Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Center and Institute Tianjin Medical University General Hospital Tianjin China; Department of Oncology Tianjin Medical University General Hospital Tianjin China.

Thoracic Cancer
|January 28, 2016
PubMed
Abstract

Insights

The transcription factor FOXO3 reduces nm23-H1 expression in lung cancer cells. This regulation occurs indirectly, offering new insights into metastasis suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Nm23-H1 is a key metastasis suppressor in various tumors.
  • Reduced nm23-H1 expression correlates with advanced non-small-cell lung cancer (NSCLC).
  • The regulatory mechanisms of nm23-H1 expression remain largely unknown.

Purpose of the Study:

  • To investigate the relationship between forkhead box (FOXO)3 activity and nm23-H1 expression in NSCLC.
  • To elucidate the role of FOXO3 in regulating nm23-H1 levels.

Main Methods:

  • Quantitative real-time PCR and Western blotting to assess nm23-H1 mRNA and protein levels.
  • FOXO3 plasmid transfection in A549 cells to modulate FOXO3 activity.
  • Dual luciferase reporter and chromatin immunoprecipitation assays to analyze nm23-H1 promoter activity and FOXO3 binding.

Main Results:

  • Activated FOXO3 significantly decreased nm23-H1 expression, while dominant-negative FOXO3 increased it.
  • Modulation of FOXO3 activity affected nm23-H1 promoter activity.
  • FOXO3 regulates nm23-H1 expression indirectly, despite a potential binding site on the promoter.

Conclusions:

  • FOXO3 acts as a negative regulator of nm23-H1 expression in NSCLC A549 cells.
  • Nm23-H1 expression is indirectly controlled by FOXO3.
  • Findings provide insights into nm23-H1 upstream regulation and potential anti-metastasis targets.
Keywords:
FoxO3metastasismetastasis suppressor genenm23‐H1non‐small‐cell lung cancer

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