Homo sapiens Transcriptome or Gene expression

Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain largely unknown. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using high throughput RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to untreated control, metformin alone down-regulated 58 genes, and up-regulated 91 genes, aspirin alone down-regulated 12 genes only, while the combination of metformin and aspirin down-regulated 656 genes, and down-regulated 449 genes (fold-change > 2, P value < 10-5). Of the top 10 genes (fold-change > 10, P value < 10-10) regulated by the combination of metformin and aspirin, PCDH18, CCL2, RASL11A, FAM111B, and BMP5, were down-regulated more than 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated more than 10-fold. The ingenuity pathway analysis (IPA) was applied to explore the top signaling pathways regulated by metformin and aspirin. The top canonical pathways, “cholesterol biosynthesis”, “cell cycle: G1/S checkpoint regulation”, and “axonal guidance signaling” were the most statistical significant pathways that were modulated by the combination of metformin and aspirin. Although the results need further functional validation, these data provide, for the first time, a transcriptional profile of pancreatic cancer cells in response to metformin and aspirin.

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