title: Phospho-ΔNp63α-responsive microRNAs contribute to the regulation of necroptosis in squamous cell carcinoma upon cisplatin exposure.
abstract: This study shows that specific microRNAs differentially regulated by ΔNp63α in cisplatin-sensitive and resistant squamous cell carcinoma (SSC) cells of larynx and tongue affect the expression of members of the necroptotic pathway CYLD, RIPK1, and MLKL. Different degrees of protein interaction between necroptotic signaling intermediates were also observed in SCC cells sensitive or resistant to cisplatin. Modulation of RIPK1 with miR-101-3p mimic or inhibitor, as well as with siRNA, or chemical inhibitors was shown to affect sensitivity of SCC cells to cisplatin. This is the first report showing the modulatory effect of ΔNp63α-responsive microRNAs on the specific members of necroptotic pathway in SCC tumor cells variably responding to platinum chemotherapy.
authors.affiliation: Head and Neck Cancer Research Division, Department of Otolaryngology/Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA. Electronic address: eratovi1@jhmi.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ratovitski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D000074749:Deubiquitinating Enzyme CYLD; D019008:Drug Resistance, Neoplasm; D020868:Gene Silencing; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009336:Necrosis; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D034741:RNA, Small Interfering; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C570693:MLKL protein, human; D011494:Protein Kinases; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D002945:Cisplatin
keywords: Cancer; Chemoresistance; Cisplatin; Necroptosis; Tumor protein p63; microRNA