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Phospho-ΔNp63α is a key regulator of the cisplatin-induced microRNAome in cancer cells

Y Huang1, A Chuang, H Hao

  • 1Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Cell Death and Differentiation
|January 29, 2011
PubMed

Insights

Chemotherapy drug cisplatin alters microRNA expression in head and neck cancer cells. This change, mediated by phospho-ΔNp63α, affects apoptosis pathways and drug response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer.
  • Cisplatin (CIS) is a common chemotherapeutic agent used in HNSCC treatment.
  • The role of ΔNp63α and its phosphorylation in HNSCC response to CIS is under investigation.

Purpose of the Study:

  • To investigate the role of phospho-ΔNp63α in regulating microRNA (miRNA) expression following cisplatin treatment in HNSCC.
  • To identify specific miRNAs deregulated by p-ΔNp63α and their downstream effects on apoptosis-related genes.

Main Methods:

  • Exposure of HNSCC cells to cisplatin (CIS).
  • Analysis of ATM-dependent phosphorylation of ΔNp63α.
  • Quantification of miRNA and mRNA expression levels.
  • Bioinformatic analysis to identify target genes.

Main Results:

  • CIS treatment induced ATM-dependent phosphorylation of ΔNp63α in HNSCC cells.
  • Phospho-ΔNp63α transcriptionally deregulated several miRNAs, including downregulation of miR-181a, miR-519a, miR-374a, and upregulation of miR-630.
  • Deregulation of these miRNAs modulated the expression of key apoptosis-related genes (e.g., TP53, ATM, CASP3, BCL2).

Conclusions:

  • MicroRNAs are critical downstream targets of p-ΔNp63α in HNSCC cells treated with cisplatin.
  • p-ΔNp63α-mediated miRNA deregulation plays a significant role in the apoptotic response to chemotherapeutic drugs.
  • These findings highlight a novel mechanism in cancer cell response to chemotherapy.

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