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Cell Rep DOI:10.1016/j.celrep.2019.04.101

The lncRNA SLNCR Recruits the Androgen Receptor to EGR1-Bound Genes in Melanoma and Inhibits Expression of Tumor Suppressor p21.

Publication TypeJournal Article
Year of Publication2019
AuthorsSchmidt, K, Carroll, JS, Yee, E, Thomas, DD, Wert-Lamas, L, Neier, SC, Sheynkman, G, Ritz, J, Novina, CD
JournalCell Rep
Volume27
Issue8
Pages2493-2507.e4
Date Published2019 May 21
ISSN2211-1247
Abstract

Melanoma is the deadliest form of skin cancer, affecting men more frequently and severely than women. Although recent studies suggest that differences in activity of the androgen receptor (AR) underlie the observed sex bias, little is known about AR activity in melanoma. Here we show that AR and EGR1 bind to the long non-coding RNA SLNCR and increase melanoma proliferation through coordinated transcriptional regulation of several growth-regulatory genes. ChIP-seq reveals that ligand-free AR is enriched on SLNCR-regulated melanoma genes and that AR genomic occupancy significantly overlaps with EGR1 at consensus EGR1 binding sites. We present a model in which SLNCR recruits AR to EGR1-bound genomic loci and switches EGR1-mediated transcriptional activation to repression of the tumor suppressor p21. Our data implicate the regulatory triad of SLNCR, AR, and EGR1 in promoting oncogenesis and may help explain why men have a higher incidence of and more rapidly progressive melanomas compared with women.

DOI10.1016/j.celrep.2019.04.101
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31116991?dopt=Abstract

Alternate JournalCell Rep
PubMed ID31116991