Abstract 1179: Global increase in ultraconserved non-coding RNA expression in pancreatic adenocarcinoma

Abstract Transcribed ultraconserved regions (T-UCRs) are a class of 482 non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in colorectal cancer, leukemia and neuroblastoma, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used qPCR to profile all 482 T-UCRs in a variety of pancreatic cancer specimens including pancreatic adenocarcinoma, chronic pancreatitis and benign/normal pancreas and in the pancreas of genetically engineered mice (P48+/Cre;LSL-KRASG12D and PDX-1-Cre;LSL-KRASG12D). Of the 257 expressed T-UCRs in the human pancreas tissues, 166 were differentially expressed in the PDAC compared to normal and adjacent benign pancreas (≥ 1.5 fold; p < 0.05). In the genetically engineered mice, 29% of the expressed T-UCRs were differentially expressed in the pancreas of old P48+/Cre;LSL-KRASG12D mice (mean age, 231 days) compared to control. In both the patient and mouse data, the vast majority of the differentially expressed T-UCRs increased with disease progression. Interestingly, the expression pattern among groups of two T-UCRs closely correlated with each other. This was to be expected for T-UCRs directly adjacent to one another in the genome, but surprisingly we found strong correlations among T-UCRs that are located on different chromosomes. This suggests that large groups of T-UCRs are co-expressed in PDAC. In vitro models that simulate the desmoplastic reaction have been shown it to alter gene expression in PDAC. In an effort to understand the mechanism responsible for this global increase in expression in PDAC, the T-UCRs were profiled in normal pancreas (HPDE) cells that were cultured on the extracellular matrix deposited by Panc-1 cells. Ninety-one T-UCRs were increased in the HPDE co-cultures (fold-change > 1.5, p< 0.05). We report a global increase in the T-UCR expression in PDAC tissues, the pancreas of genetically engineered mice and in HPDE cells co-cultured with Panc-1 cells. The ability of the MAP kinase and TGF-β signaling pathways to regulate T-UCR expression will be investigated in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1179. doi:10.1158/1538-7445.AM2011-1179