title: The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes.
abstract: The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated 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, colony formation, 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 2-5, antiapoptotic gene X-linked inhibitor of apoptosis, and baculoviral IAP repeat-containing 7 were all up-regulated in SPRIGHTLY-expressing melanocytes, whereas the proapoptotic tumor suppressor gene DPPIV/CD26 was down-regulated, followed by an increase in extracellular signal-regulated kinase 1/2 phosphorylation, suggesting an increase in mitogen-activated protein kinase activity. Because down-regulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV down-regulation may play an important role in melanoma pathobiology. Together, these findings provide important insights into how SPRIGHTLY regulates cell proliferation and anchorage-independent colony formation in primary human melanocytes.
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mazar
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Bongyong
authors.initials: B
authors.lastname: Lee
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Sawada
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Li
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: John
authors.initials: J
authors.lastname: Shelley
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Govindarajan
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Dwight
authors.initials: D
authors.lastname: Towler
authors.affiliation: Garvan Institute of Medical Research and St. Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia.
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Garvan Institute of Medical Research and St. Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia.
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Dinger
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando, Florida, USA. Electronic address: rperera@sanfordburnham.org.
authors.forename: Ranjan J
authors.initials: RJ
authors.lastname: Perera
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D020935:MAP Kinase Signaling System; D013058:Mass Spectrometry; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D064111:Minichromosome Maintenance Complex Component 2 / Q000378:metabolism; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D019394:Ki-67 Antigen; D062085:RNA, Long Noncoding; C000605823:long noncoding RNA SPRY4-IT1, human; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2
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