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 language | English (US) |
|---|---|
| Pages (from-to) | 3938-3947 |
| Number of pages | 10 |
| Journal | Cell Cycle |
| Volume | 10 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 15 2011 |
| Externally published | Yes |
Keywords
- Apoptosis
- Autophagy
- Cell death
- Cisplatin resistance
- MicroRNA
- Squamous cell carcinoma
- Tumor protein p63
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology