title: Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure.
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, CASP2, and CASP3 mRNAs via pairing with their respective 'recognition' sequences. Cisplatin exposure modulated the levels of target proteins (reduced BCL2, AKT1, ATG16L2, and ULK2, while 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 up regulation of MDM4 levels and down regulation 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.
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Huang
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Chuang
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ratovitski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001343:Autophagy / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; C574934:MIRN885 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C495901:TP53 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D008156:Luciferases; D002945:Cisplatin
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