ARNTL hypermethylation promotes tumorigenesis and inhibits cisplatin sensitivity by activating CDK5 transcription in nasopharyngeal carcinoma

摘要: Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) NPC. We employed bisulfite pyrosequencing to determine epigenetic change ARNTL NPC cell lines and tissues. mRNA protein expression tissues were detected by real-time PCR western blotting. Then, constructed overexpressing knocked down explore its function effect on chemotherapy sensitivity cisplatin vitro vivo. Finally, investigated potential molecular mechanism set enrichment analysis (GSEA), dual Luciferase reporter assay chromatin immunoprecipitation assay. was hypermethylated, significantly down-regulated When treated 5-aza-2′-deoxycytidine, up-regulated. Overexpression could suppress cells proliferation vivo while silencing using shRNA achieved opposite results. GSEA found that associated with cycle ectopic overexpression induce G2-M phase arrest. identified validated cyclin-dependent kinase 5 (CDK5) as targeting transiently infected ARNTL-overexpression PENTER-vector or PENTER-CDK5 plasmids, later reverse suppressive effects proliferation. Moreover, enhanced cells. suppresses enhances CDK5. may represent a novel therapeutic target