Metabolomics defines the function of microRNA-1291 in pancreatic tumor cell metabolism and tumorigenesis

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NCI	sRNA-2

Authors

• H.C. Bi
• K.W. Krausz
• F. Li
• C.H. Johnson
• Y.Z. Pan
• A.M. Yu
• F.J. Gonzalez

Abstract

Previously, we established a miR-1291 stably transfected cell line and observed that it exhibited G2/M arrest. In addition, we saw suppressed tumorigenesis when Panc-1 cells (human pancreatic tumor cell) overexpressing miR-1291 were inoculated into immunodeficient nude mice. In order to investigate the impact of miR-1291 on cell metabolism and reveal possible biomarkers for tumorigenesis, miR-1291 and empty vector (control) stably transfected Panc-1 cells were subjected to metabolomic analyses using ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. PCA and PLS-DA models were built to identify biomolecules that were significantly different between the two cell lines. Some of these metabolites were identified to be 1-methylnicotinamide, L-carnitine and acylcarnitines, and were upregulated in the miR1291 transfected Panc-1 cells. Gene expression of the related enzymes including Nicotinamide N-methyltransferase (NNMT) and palmitoyltransferase 1C and IA (CPT1C, CPT1A) were also significantly increased. Future work will involve metabolomic analysis of biofluids and tissues from miR-1291 and empty vector transfected Panc-1 cell xenograft tumor mouse to reveal further biomarkers of tumorigenesis. Metabolomics has thus aided in understanding the impact of miR on tumor cell metabolism and revealed possible biomarkers for tumorigenesis that hold the promise as novel targets for pancreatic cancer therapy or prevention.

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