Ratovitski Edward A
Head and Neck Cancer Research Division, Department of Otolaryngology/Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
FEBS Lett. 2015 May 22;589(12):1352-8. doi: 10.1016/j.febslet.2015.04.020. Epub 2015 Apr 21.
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.
本研究表明，在喉和舌的顺铂敏感及耐药鳞状细胞癌（SSC）细胞中，由ΔNp63α差异调节的特定微小RNA影响坏死性凋亡途径CYLD、RIPK1和MLKL成员的表达。在对顺铂敏感或耐药的SCC细胞中也观察到坏死性凋亡信号中间体之间不同程度的蛋白质相互作用。用miR-101-3p模拟物或抑制剂、siRNA或化学抑制剂调节RIPK1，显示会影响SCC细胞对顺铂的敏感性。这是首份报告显示ΔNp63α反应性微小RNA对在铂类化疗中反应各异的SCC肿瘤细胞坏死性凋亡途径特定成员的调节作用。
