<i>AC016745.3</i> Regulates the Transcription of AR Target Genes by Antagonizing NONO

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examine...

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Autores principales: Yali Lu, Xuechao Wan, Wenhua Huang, Lu Zhang, Jun Luo, Dujian Li, Yan Huang, Yao Li, Yaoting Xu
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/7b223a770eb44a31a300146ebe6735d5
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Sumario:The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA <i>AC016745.3</i> in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of <i>AC016745.3</i> expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of <i>AC016745.3</i> inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind <i>AC016745.3</i>. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that <i>AC016745.3</i> can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that <i>AC016745.3</i> can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of <i>AC016745.3</i> expression can enhance NONO’s promotion effect on AR.