title: Delta Np63 alpha – Responsive microRNA Modulate the Expression of Metabolic Enzymes.
abstract: MicroRNAs, whose transcription is regulated by members of the tumor protein p53 family, modulate the expression of numerous metabolic enzymes, significantly altering tumor cell response to chemotherapeutic treatments. The role for ΔNp63α-regulated microRNAs in regulation of cell cycle arrest, apoptosis and autophagy in squamous cell carcinoma (SCC) cells upon cisplatin exposure has been reported. The current study indicated that the selected microRNA targets differentially regulated by ΔNp63α in cisplatin-sensitive and cisplatin-resistant SCC cells could alter the expression of a few metabolic enzymes, thereby potentially contributing to the metabolic changes in SCC cells upon cisplatin exposure. Finally, the modulation of specific targets (e.g., SREBF2, AKT2, G6PD, CPS1, FADS1, and ETNK1) using a combination of microRNA mimics and siRNA silencing has shown that a suppression of these metabolic factors/ enzymes could confer a sensitivity of SCC cells to cisplatin. Thus, the Δ Np63α-regulated microRNAs were found to regulate the levels of several metabolic factors and enzymes, thereby potentially contributing to the response of larynx and tongue-derived SCC cells to platinum chemotherapy.
authors.affiliation: Head and Neck Cancer Research Division, Cancer Research Building II, 1550 Orleans Street, Baltimore, MD 21231, USA. eratovi1@jhmi.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ratovitski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D000090943:Delta-5 Fatty Acid Desaturase; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000090943:Delta-5 Fatty Acid Desaturase; D035683:MicroRNAs; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C000716847:FADS1 protein, human; D002945:Cisplatin