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

Y. Huang, A. Chuang, Haiping Hao, C. Talbot, T. Sen, B. Trink, David Sidransky, E. Ratovitski

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinoma (HNSCC) cells exposed to cisplatin (CIS) displayed a dramatic ATM-dependent phosphorylation of ΔNp63α that leads to the transcriptional regulation of downstream mRNAs. Here, we report that phospho (p)-ΔNp63α transcriptionally deregulates miRNA expression after CIS treatment. Several p-ΔNp63α-dependent microRNA species (miRNAs) were deregulated in HNSCC cells upon CIS exposure, including miR-181a, miR-519a, and miR-374a (downregulated) and miR-630 (upregulated). Deregulation of miRNA expression led to subsequent modulation of mRNA expression of several targets (TP53-S46, HIPK2, ATM, CDKN1A and 1B, CASP3, PARP1 and 2, DDIT1 and 4, BCL2 and BCL2L2, TP73, YES1, and YAP1) that are involved in the apoptotic process. Our data support the notion that miRNAs are critical downstream targets of p-ΔNp63α and mediate key pathways implicated in the response of cancer cells to chemotherapeutic drugs.

Original languageEnglish (US)
Pages (from-to)1220-1230
Number of pages11
JournalCell Death and Differentiation
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Keywords

  • cisplatin
  • DICER1
  • microRNA
  • p63
  • squamous cell carcinomas

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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