Abstract A09: The long noncoding RNA SPRIGHTLY regulates cell proliferation in primary human melanocytes

Abstract

Abstract The long non-coding RNA (lncRNA) SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene is upregulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, invasion, and development of a multinucleated dendritic-like phenotype. RNA sequencing and mass spectrometric analysis of SPRIGHTLY-expressing cells revealed changes in the expression of genes involved in cell proliferation, apoptosis, chromosome organization, regulation of DNA damage responses, and cell cycle. The proliferation marker Ki67, minichromosome maintenance genes (MCM2-5), and the anti-apoptotic genes X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing 7 (livin) were upregulated in SPRIGHTLY-expressing melanocytes, while the pro-apoptotic tumor suppressor gene DPPIV/CD26 was downregulated. Since downregulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV downregulation may play an important role in melanoma pathobiology. These findings provide novel insights into how SPRIGHTLY regulates proliferation, and apoptosis in primary human melanocytes. Citation Format: Wei Zhao, Joseph Mazar, Bongyong Lee, Junko Sawada, Jian-Liang Li, John Shelley, Subramaniam Govindarajan, Dwight Towler, John S. Mattick, Masanobu Komatsu, Marcel E. Dinger, Ranjan J. Perera. The long noncoding RNA SPRIGHTLY regulates cell proliferation in primary human melanocytes. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A09.