ARLNC1 is expressed in prostate cancer and stabilizes the AR transcript to promote AR signaling.
Major finding: ARLNC1 is expressed in prostate cancer and stabilizes the AR transcript to promote AR signaling.
Concept: AR binds to the ARLNC1 promoter to upregulate ARLNC1 in an oncogenic positive feedback loop.
Impact: ARLNC1 may be a potential therapeutic target to suppress AR signaling in patients with prostate cancer.
Androgen receptor (AR) signaling is critical for prostate tumor progression and maintenance, but the role of long noncoding RNAs (lncRNA) in AR signaling is not well understood. In order to identify AR-regulated lncRNAs involved in prostate tumorigenesis, Zhang, Pitchiaya, Cieślik, and colleagues performed RNA sequencing of prostate cancer cell lines and patient tissue samples. A total of 342 AR-regulated lncRNAs were identified, including ARLNC1, one of the most differentially expressed lncRNAs compared with normal tissue. Analysis of data from The Cancer Genome Atlas revealed that ARLNC1 expression was highly specific to prostate cancer, and it was overexpressed in both localized and metastatic tumors. AR bound to the promoter region of ARLNC1 to directly promote its expression. In addition, ARLNC1 enhanced AR signaling by binding to the 3' UTR of AR and stabilizing the AR transcript, maintaining a positive feedback loop to potentiate AR signaling. ARLNC1 and AR colocalized in prostate tumors, suggesting that this positive feedback loop occurs in vivo, and blocking the ARLNC1–AR interaction reduced AR signaling. Inhibition of ARLNC1 suppressed the growth of AR-dependent prostate cancer cells in vitro and delayed the growth of prostate cancer xenografts in vivo. In addition to demonstrating an oncogenic role for ARLNC1 in enhancing AR signaling to promote prostate tumorigenesis, these findings suggest that ARLNC1 may be a potential therapeutic target in patients with prostate cancer.
Zhang Y, Pitchiaya S, Cieślik M, Niknafs YS, Tien JC, Hosono Y, et al. Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression. Nat Genet 2018;50:814–24.
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