Abstract
Abstract Recent advances in sequencing technology have been increasing our understanding of non-protein coding regions in the mammalian genome. There is growing recognition that the majority of mammalian genome produces long non-coding RNA (lncRNA). Generally, their expression is lower than protein-coding genes and they are strikingly tissue-specific. Several studies have shown that they function in various aspects of cell biology. Abnormal expression and dysregulation of lncRNAs are associated with various types of cancer including pancreatic ductal adenocarcinoma (PDAC), which has the worst prognosis of the major cancers, with a 5-year survival rate of 5%, due to difficulties in early detection and limited therapeutic options. Although lncRNAs play important roles in cancer, they have not been extensively studied in PDAC. The goal of this study is to identify PDAC-related lncRNAs and characterize their functions in pancreatic cancer cells. Recently, we identified a potentially important lncRNA, PANCRNA1 (pancreatic cancer RNA 1), in PDAC progression through re-annotation of whole genome transcript RNA sequencing data of PDAC tissue samples from sequence read archive (SRA). Overexpressed candidates were determined in both early stage and metastatic PDAC tissue samples. PANCRNA1 shows a statistically significant higher expression profile in PDAC tissue samples. Its expression in different pancreatic cancer cell lines was confirmed (BxPC-3, MiaPaca-2 and Panc-1) by RT-qPCR. In order to investigate the effect of PANCRNA1 on pancreatic cancer cells, its expression was transiently knocked down using targeting siRNA. Statistically significant changes were reported on cell phenotype by measuring the rate of cell proliferation and motility. PANCRNA1 knock down reduced proliferation and cell motility in wound healing assays as compared to scrambled siRNA controls. To determine potential mechanisms underlying the observed effects of PANCRNA1 on pancreatic cancer cells, changes in epidermal growth factor receptor (EGFR) signaling, which contributes to pancreatic tumor cell proliferation, evasion of apoptosis, angiogenesis and metastasis were investigated. Knock down of PANCRNA1, decreased both EGFR transcript and protein levels. These results provide the first evidence for the expression and the function of PANCRNA1 in pancreatic cancer and the motivation for future studies to further elucidate its mechanisms of action and determine its possible application as a marker and target. Citation Format: Husna Karaboga, Philip Jonsson, Yu Liu, Chin-Yo Lin. Long noncoding RNA PANCRNA1 is a novel regulator of cell growth and motility in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A07.
Published Version
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