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

Head and neck squamous cell carcinoma (HNSCC) cells exposed to cisplatin (CIS) displayed a dramatic ATM-dependent phosphorylation of Delta Np63 alpha that leads to the transcriptional regulation of downstream mRNAs. Here, we report that phospho (p)-Delta Np63 alpha transcriptionally deregulates miRNA expression after CIS treatment. Several p-Delta Np63 alpha-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-Delta Np63 alpha and mediate key pathways implicated in the response of cancer cells to chemotherapeutic drugs. Cell Death and Differentiation (2011) 18, 1220-1230; doi:10.1038/cdd.2010.188; published online 28 January 2011