Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure
| Autor: | Alice Y. Chuang, Yiping Huang, Edward A. Ratovitski |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
Antineoplastic Agents Apoptosis Cell Cycle Proteins Mitochondrion Biology Genes Reporter Report Cell Line Tumor Proto-Oncogene Proteins microRNA Autophagy Transcriptional regulation medicine Humans RNA Messenger Viability assay Phosphorylation Luciferases Molecular Biology Cisplatin Tumor Suppressor Proteins Nuclear Proteins Cell Biology Mitochondria Cell biology Gene Expression Regulation Neoplastic MicroRNAs Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm Carcinoma Squamous Cell Cancer research Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins Transcription Factors Developmental Biology medicine.drug |
| Zdroj: | Cell Cycle. 10:3938-3947 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.10.22.18107 |
| Popis: | 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, 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 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. |
| Databáze: | OpenAIRE |
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