Integrated Analysis Of Differential MiRNA And MRNA Expression Profiles In Human Radioresistant And Radiosensitive Nasopharyngeal Carcinoma Cells

[Objective] Nasopharyngeal carcinoma (NPC) is an endemic disease in southern China and Southeast Asia, the primary treatment for NPC is radiotherapy.Radioresistance is the important reason of patient survival. The purpose of this study was to identify miRNAs and genes involved in NPC radioresistance, and explore the underlying mechanisms in the development of radioresistance to provide a theoretical and experimental evidence for its clinical trial.\[Materials and Methods] We used microarrays to compare the differences of both miRNA and mRNA expression profiles in the radioresistant NPC CNE2-IR and radiosensitive NPC CNE2cells, applied qRT-PCR to confirm the reliability of microarray data, adopted databases prediction and anticorrelated analysis of miRNA and mRNA expression to identify the miRNA target genes, and employed bioinformatics tools to examine the functions and pathways in which miRNA target genes are involved, and construct a miRNA-target gene regulatory network. We further investigated the roles of miRNA-23a and its target gene IL-8in the NPC radioresistance.[Results] The main findings were fivefold:(1) fifteen differential miRNAs and372differential mRNAs were identified, and the reliability of microarray data was validated for randomly selected nine miRNAs and eight genes;(2)174miRNA target were identified, and most of their functions and regulating pathways were related to tumor therapeutic resistance;(3) a posttranscriptional regulatory network including375miRNA-target gene pairs was constructed, in which the ten genes were coregulated by the six miRNAs;(4) IL-8was a direct target of miRNA-23a, the expression levels of IL-8were elevated in the radioresistant NPC tissues and showed inverse correlation with miRNA-23a expression, and genetic upregulation of miRNA-23a and antibody neutralization of secretory IL-8could reduce NPC cells radioresistance.[Conclusions] We identified fifteen differential miRNAs and372differential mRNAs in the radioresistant NPC cells, constructed a posttranscriptional regulatory network including375miRNA-target gene pairs, identified the ten target genes coregulated by the six miRNAs, for the first time discovered IL-8as the target genes of miRNA-23a, and validated that downregulated miRNA-23a was involved in NPC radioresistance through directly targeting IL-8. Our data form a basis for further investigating the mechanisms of NPC radioresistance.