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

The cisplatin-induced ATM-dependent phosphorylated (p)-Delta Np63 alpha 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-Delta Np63 alpha-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2 and CASP3 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 Delta Np63 alpha 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.