Oncotarget

Research Papers:

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

Joseph Mazar _, Wei Zhao, Ahmad M. Khalil, Bongyong Lee, John Shelley, Subramaniam S. Govindarajan, Fumiko Yamamoto, Maya Ratnam, Muhammad Nauman Aftab, Sheila Collins, Brian N. Finck, Xianlin Han, John S. Mattick, Marcel E. Dinger and Ranjan J. Perera

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Oncotarget. 2014; 5:8959-8969. https://doi.org/10.18632/oncotarget.1863

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Abstract

Joseph Mazar1, Wei Zhao1, Ahmad M. Khalil2, Bongyong Lee1, John Shelley1, Subramaniam S. Govindarajan1, Fumiko Yamamoto1, Maya Ratnam2, Muhammad Nauman Aftab1, Sheila Collins1, Brian N. Finck3, Xianlin Han1, John S. Mattick4, Marcel E. Dinger4, and Ranjan J. Perera1*

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

Correspondence:

Ranjan J. Perera, email:

Keywords: long noncoding RNA, melanoma

Received: January 23, 2014 Accepted: March 24, 2014 Published: March 26, 2014

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.


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