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The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells

Abstract

Expression of the long noncoding RNA (lncRNA) SPRY4-IT1 is low in normal human melanocytes but high in melanoma cells. siRNA knockdown of SPRY4-IT1 blocks melanoma cell invasion and proliferation, and increases apoptosis. To investigate its function further, we affinity purified SPRY4-IT1 from melanoma cells and used mass spectrometry to identify the protein lipin 2, an enzyme that converts phosphatidate to diacylglycerol (DAG), as a major binding partner. SPRY4-IT1 knockdown increases the accumulation of lipin2 protein and upregulate the expression of diacylglycerol O-acyltransferase 2 (DGAT2) an enzyme involved in the conversion of DAG to triacylglycerol (TAG). When SPRY4-IT1 knockdown and control melanoma cells were subjected to shotgun lipidomics, an MS-based assay that permits the quantification of changes in the cellular lipid profile, we found that SPRY4-IT1 knockdown induced significant changes in a number of lipid species, including increased acyl carnitine, fatty acyl chains, and triacylglycerol (TAG). Together, these results suggest the possibility that SPRY4-IT1 knockdown may induce apoptosis via lipin 2-mediated alterations in lipid metabolism leading to cellular lipotoxicity.

Type Journal
ISBN 1949-2553 (Electronic) 1949-2553 (Linking)
Authors Mazar, J.; Zhao, W.; Khalil, A. M.; Lee, B.; Shelley, J.; Govindarajan, S. S.; Yamamoto, F.; Ratnam, M.; Aftab, M. N.; Collins, S.; Finck, B. N.; Han, X.; Mattick, J. S.; Dinger, M. E.; Perera, R. J.;
Publisher Name Oncotarget
Published Date 2014-01-01
Published Volume 5
Published Issue 19
Published Pages 8959-69
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/25344859
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/12621