Doxorubicin downregulates cell cycle regulatory hub genes in breast cancer cells

Mano Chitra Karthikeyan1, Chandhru Srinivasan1, Kowsika Prabhakar1

  • 1Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620 024, India.

Insights

This study identified nine key genes crucial for breast cancer (BC) progression. Doxorubicin (DOX) treatment effectively reduced the expression of these genes, reinforcing DOX

Area of Science:

  • Oncology
  • Genetics
  • Bioinformatics

Background:

  • Breast cancer (BC) is a leading global cancer with complex developmental mechanisms.
  • Identifying key genes is crucial for advancing BC therapeutics.
  • Doxorubicin (DOX) is a common chemotherapy agent for BC.

Purpose of the Study:

  • To investigate the influence of doxorubicin (DOX) on key genes in breast cancer (BC).
  • To identify novel therapeutic targets for BC treatment through bioinformatic analysis.

Main Methods:

  • Meta-analysis of publicly available breast cancer gene expression datasets from the Gene Expression Omnibus (GEO).
  • Identification of common differentially expressed genes (DEGs) using GEO2R.
  • Bioinformatic analysis including KEGG pathway enrichment, Cytoscape for hub gene identification, and validation using GEPIA and UALCAN databases.
  • Quantitative real-time PCR (qRT-PCR) to confirm gene expression changes in BC cell lines post-DOX treatment.

Main Results:

  • A total of 23 common DEGs were identified, with nine upregulated genes identified as potential hub genes (NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1).
  • These hub genes were significantly enriched in the cell cycle pathway and were associated with unfavorable overall survival in BC patients across all subclasses.
  • qRT-PCR confirmed that DOX treatment significantly reduced the expression of these nine hub genes in BC cell lines.

Conclusions:

  • The identified hub genes play a critical role in breast cancer progression and are targeted by doxorubicin.
  • Doxorubicin remains an effective therapeutic option for breast cancer.
  • Developing modified doxorubicin formulations could potentially reduce toxicity and overcome resistance, enhancing its efficacy.

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