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Oncotarget. 2014 Oct 15;5(19):8959-69.

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

Author information

1
Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA.
2
Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
3
Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.

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.

PMID:
25344859
PMCID:
PMC4253410
DOI:
10.18632/oncotarget.1863
[Indexed for MEDLINE]
Free PMC Article

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