AI Article Synopsis
- Melanoma is the most dangerous type of skin cancer, impacting men more severely than women, possibly due to differences in androgen receptor (AR) activity.
- Recent research shows that AR, in coordination with EGR1, interacts with a long non-coding RNA called SLNCR to promote cancer cell growth by regulating key genes.
- The study proposes that SLNCR helps AR bind to EGR1 sites in the genome, shifting EGR1's role from activating a tumor suppressor gene (p21) to repressing it, which could explain the higher rates of melanoma progression in men.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668037 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2019.04.101 | DOI Listing |
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