Phospho-ΔNp63α/microRNA network modulates epigenetic regulatory enzymes in squamous cell carcinomas

Edward A. Ratovitski

Research output: Contribution to journalArticlepeer-review

Abstract

The tumor protein (TP) p63/microRNAs functional network may play a key role in supporting the response of squamous cell carcinomas (SCC) to chemotherapy. We show that the cisplatin exposure of SCC-11 cells led to upregulation of miR-297, miR-92b-3p, and miR-485-5p through a phosphorylated ΔNp63α-dependent mechanism that subsequently modulated the expression of the protein targets implicated in DNA methylation (DNMT3A), histone deacetylation (HDAC9), and demethylation (KDM4C). Further studies showed that mimics for miR-297, miR-92b-3p, or miR-485-5p, along with siRNA against and inhibitors of DNMT3A, HDAC9, and KDM4C modulated the expression of DAPK1, SMARCA2, and MDM2 genes assessed by the quantitative PCR, promoter luciferase reporter, and chromatin immunoprecipitation assays. Finally, the above-mentioned treatments affecting epigenetic enzymes also modulated the response of SCC cells to chemotherapeutic drugs, rendering the resistant SCC cells more sensitive to cisplatin exposure, thereby providing the groundwork for novel chemotherapeutic venues in treating patients with SCC.

Original languageEnglish (US)
Pages (from-to)749-761
Number of pages13
JournalCell cycle (Georgetown, Tex.)
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2014

Keywords

  • Chemoresistance
  • DNA methylation
  • Epigenetic regulation
  • Histone deacetylation
  • Histone demethylation
  • microRNA
  • Squamous cell carcinomas
  • TP63

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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