Journal
CELL REPORTS
Volume 30, Issue 2, Pages 541-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.12.011
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Funding
- NIH [R01 CA140986, R01 CA185151, R35 GM122532]
- Claudia Adams Barr Award
- Intramural Research Program of the NIH, Center for Cancer Research, the National Cancer Institute (NCI) [NIH 1 ZIA BC011585]
- [T32 AI007386]
- [T32 CA009156]
- NATIONAL CANCER INSTITUTE [ZIABC011585] Funding Source: NIH RePORTER
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Long non-coding RNAs (lncRNAs) are critical regulators of numerous physiological processes and diseases, especially cancers. However, development of lncRNA-based therapies is limited because the mechanisms of many lncRNAs are obscure, and interactions with functional partners, including proteins, remain uncharacterized. The lncRNA SLNCR1 binds to and regulates the androgen receptor (AR) to mediate melanoma invasion and proliferation in an androgen-independent manner. Here, we use biochemical analyses coupled with selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing to show that the N-terminal domain of AR binds a pyrimidine-rich motif in an unstructured region of SLNCR1. This motif is predictive of AR binding, as we identify an AR-binding motif in lncRNA HOXA11-AS-203. Oligonucleotides that bind either the AR N-terminal domain or the AR RNA motif block the SLNCRI-AR interaction and reduce SLNCRI-mediated melanoma invasion. Delivery of oligos that block SLNCR1-AR interaction thus represent a plausible therapeutic strategy.
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