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Screening of FOXD3 targets in lung cancer via bioinformatics analysis

Wenhua Jiang1, Pengfei Liu2,3,4,5,6, Xiaodong Li1

  • 1Department of Radiotherapy, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.

Oncology Letters
|February 14, 2018
PubMed

Insights

Forkhead box D3 (FOXD3) plays a key role in lung cancer by regulating tumor cell growth and migration. This study identified FOXD3 targets, including AURKA and NOS3, offering insights for lung cancer diagnosis and therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Lung cancer remains a leading cause of cancer-related mortality worldwide.
  • Understanding the molecular mechanisms driving lung cancer progression is crucial for developing effective therapies.
  • Forkhead box D3 (FOXD3) is a transcription factor implicated in various cellular processes, but its specific role in lung cancer requires further elucidation.

Purpose of the Study:

  • To investigate the molecular targets of Forkhead box D3 (FOXD3) in lung cancer.
  • To identify genes and pathways regulated by FOXD3 in lung cancer cells.
  • To provide potential diagnostic and therapeutic targets for lung cancer.

Main Methods:

  • Downloaded gene expression profile (GSE64513) from the Gene Expression Omnibus database.
  • Utilized R's limma package to identify differentially expressed genes (DEGs) between FOXD3-knockout and normal A549 lung cancer cells.
  • Employed Replicate Multivariate Analysis of Transcript Splicing software to identify alternative splicing genes (ASGs).
  • Performed functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery.
  • Constructed a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes and visualized with Cytoscape.

Main Results:

  • Identified 1,853 DEGs and 2,249 ASGs in FOXD3-knockout A549 cells compared to normal cells.
  • DEGs were enriched in 338 Gene Ontology (GO) terms and 21 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
  • ASGs were enriched in 470 GO terms and 22 KEGG pathways.
  • Found 199 overlapping genes between DEGs and ASGs, forming a PPI network with 97 nodes and 115 interactions.
  • Identified potential FOXD3 target genes, including AURKA and NOS3.

Conclusions:

  • FOXD3 plays a significant role in regulating lung tumor cell growth, migration, and proliferation.
  • AURKA and NOS3 are identified as potential direct or indirect targets of FOXD3 in lung cancer.
  • These findings contribute to understanding FOXD3's function in lung cancer and suggest potential therapeutic strategies.
Keywords:
Gene Expression Omnibus databasebioinformaticsforkhead box D3lung cancer

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