title: The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region.
abstract: Long non-coding RNAs (lncRNAs) have been implicated in numerous physiological processes and diseases, most notably cancers. However, little is known about the mechanism of many functional lncRNAs. We identified an abundantly expressed lncRNA associated with decreased melanoma patient survival. Increased expression of this lncRNA, SLNCR1, mediates melanoma invasion through a highly conserved sequence similar to that of the lncRNA SRA1. Using a sensitive technique we term RATA (RNA-associated transcription factor array), we show that the brain-specific homeobox protein 3a (Brn3a) and the androgen receptor (AR) bind within and adjacent to SLNCR1's conserved region, respectively. SLNCR1, AR, and Brn3a are specifically required for transcriptional activation of matrix metalloproteinase 9 (MMP9) and increased melanoma invasion. Our observations directly link AR to melanoma invasion, possibly explaining why males experience more melanoma metastases and have an overall lower survival in comparison to females.
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.
authors.forename: Karyn
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.
authors.forename: Cailin E
authors.initials: CE
authors.lastname: Joyce
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Buquicchio
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Brown
authors.affiliation: Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Belfer Office for Dana-Farber Innovation, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Distel
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: chyoon@bics.bwh.harvard.edu.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Yoon
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA. Electronic address: carl_novina@dfci.harvard.edu.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Novina
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D011944:Receptors, Androgen; D016019:Survival Analysis; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
chemical_list: C410798:AR protein, human; C494188:POU4F1 protein, human; D062085:RNA, Long Noncoding; D011944:Receptors, Androgen; D050819:Transcription Factor Brn-3A; C000624628:long non-coding RNA SLNCR1, human; D020780:Matrix Metalloproteinase 9
keywords: MMP9; hormone receptor; invasion; long non-coding RNA; melanoma; metastasis