Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure

Yiping Huang, Alice Y. Chuang, Edward A. Ratovitski

Research output: Contribution to journalArticle

Abstract

The cisplatin-induced ATM-dependent phosphorylated (p)-ΔNp63α plays an important role in transcriptional regulation of specific genes encoding mRNAs and microRNAs (miRs) implicated in cell death, cell survival and chemoresistance. The p-ΔNp63α-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP 2 and CASP 3 mRNAs via pairing with their respective "recognition" sequences. Cisplatin exposure modulated the levels of target proteins (it reduced BCL2, AKT1, ATG16L2 and ULK2, while it activated MDM4) in cisplatin-sensitive wild-type ΔNp63α cells, leading to distinct changes in cell viability. Finally, miR-885-3p modulated the cisplatin-induced TP53- dependent mitochondrial apoptosis by upregulation of MDM4 levels and downregulation of BCL2 levels in mitochondria. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/ or autophagy in squamous cell carcinoma cells upon cisplatin exposure.

Original languageEnglish (US)
Pages (from-to)3938-3947
Number of pages10
JournalCell Cycle
Volume10
Issue number22
DOIs
StatePublished - Nov 15 2011

Keywords

  • Apoptosis
  • Autophagy
  • Cell death
  • Cisplatin resistance
  • MicroRNA
  • Squamous cell carcinoma
  • Tumor protein p63

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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