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

Cell Rep. 2019 May 21;27(8):2493-2507.e4. doi: 10.1016/j.celrep.2019.04.101.


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 p21Waf1/Cip1. 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.

Keywords: CDKN1A; EGR1; Waf1/Cip1; androgen receptor; linc00673; long non-coding RNA; melanoma; metastasis; p21; proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Early Growth Response Protein 1 / chemistry
  • Early Growth Response Protein 1 / metabolism*
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ligands
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Protein Binding
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Ligands
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Receptors, Androgen
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • long non-coding RNA SLNCR1, human