Loss of Long Noncoding RNA <i>NXTAR</i> in Prostate Cancer Augments Androgen Receptor Expression and Enzalutamide Resistance.

ABSTRACT: Androgen receptor (AR) signaling continues to play a dominant role in all stages of prostate cancer, including castration-resistant prostate cancers (CRPC) that have developed resistance to second generation AR antagonists such as enzalutamide. In this study, we identified a long noncoding RNA (lncRNA), NXTAR (LOC105373241) that is located convergent with the AR gene and is repressed in human prostate tumors and cell lines. NXTAR bound upstream of the AR promoter and promoted EZH2 recruitment, causing significant loss of AR (and AR-V7) expression. Paradoxically, AR bound the NXTAR promoter, and inhibition of AR by the ACK1/TNK2 small molecule inhibitor (R)-9b excluded AR from the NXTAR promoter. The histone acetyltransferase GCN5 bound and d

SUBMITTER: Ghildiyal R 

PROVIDER: S-EPMC8732311 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature