The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region

Karyn Schmidt; Cailin E Joyce; Frank Buquicchio; Adam Brown; Justin Ritz; Robert J Distel; Charles H Yoon; Carl D Novina

doi:10.1016/j.celrep.2016.04.018

The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region

Cell Rep. 2016 May 31;15(9):2025-37. doi: 10.1016/j.celrep.2016.04.018. Epub 2016 May 19.

Authors

Karyn Schmidt¹, Cailin E Joyce¹, Frank Buquicchio¹, Adam Brown², Justin Ritz³, Robert J Distel⁴, Charles H Yoon⁵, Carl D Novina⁶

Affiliations

¹ 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.
² Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
³ Harvard School of Public Health, Boston, MA 02115, USA.
⁴ Belfer Office for Dana-Farber Innovation, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
⁵ Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: chyoon@bics.bwh.harvard.edu.
⁶ 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.

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.

Keywords: MMP9; hormone receptor; invasion; long non-coding RNA; melanoma; metastasis.

MeSH terms

Base Sequence
Cell Line, Tumor
Conserved Sequence / genetics*
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
Melanoma / genetics*
Melanoma / pathology*
Models, Biological
Neoplasm Invasiveness
Promoter Regions, Genetic / genetics
Protein Binding / genetics
RNA, Long Noncoding / genetics*
Receptors, Androgen
Survival Analysis
Transcription Factor Brn-3A / metabolism
Transcription, Genetic
Up-Regulation / genetics

Substances

AR protein, human
POU4F1 protein, human
RNA, Long Noncoding
Receptors, Androgen
Transcription Factor Brn-3A
long non-coding RNA SLNCR1, human
Matrix Metalloproteinase 9

Abstract

MeSH terms

Substances

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