Transcriptome profiling in oral cavity and esophagus tissues from (S)-N'-nitrosonornicotine-treated rats reveals candidate genes involved in human oral cavity and esophageal carcinogenesis.

摘要: Recently, we have shown that (S)-N'-Nitrosonornicotine [(S)-NNN], the major form of NNN in tobacco products, is a potent oral cavity and esophageal carcinogen rats. To determine early molecular alterations induced by (S)-NNN mucosa, administered to rats drinking water for 10 wk global gene expression were analyzed RNA sequencing. At false discovery rate P-value < 0.05 fold-change ≥2, found level 39 genes 69 esophagus. Validation sequencing results qRT-PCR assays revealed high cross-platform concordance. The most significant impact exposure was alteration involved immune regulation (Aire, Ctla4, CD80), inflammation (Ephx2 Inpp5d) cancer (Cdkn2a, Dhh, Fetub B, Inpp5d, Ly6E, Nr1d1, Wnt6). Consistent with findings rat tissues, deregulated, albeit different degrees, immortalized keratinocytes treated non-treated premalignant cells malignant head neck squamous cells. Furthermore, interrogation TCGA data sets showed deregulated tissues (Fetub, Ly6e, Cacna1c, Cd80, Dgkg) are also altered tumors. Overall, our provide novel insights into changes and, therefore, could contribute development biomarkers detection prevention (S)-NNN-associated cancers. © 2016 Wiley Periodicals, Inc.