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Prostate. 2019 Sep;79(12):1362-1377. doi: 10.1002/pros.23840. Epub 2019 Jul 3.

A novel androgen-reduced prostate-specific lncRNA, PSLNR, inhibits prostate-cancer progression in part by regulating the p53-dependent pathway.

Author information

1
State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai, PR China.
2
Department of Urology, Shanghai Four People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, PR China.

Abstract

BACKGROUND:

Prostate cancer (PCa) is one of the most common cancers in males in China. Long noncoding RNAs (lncRNAs) reportedly play crucial roles in human cancer progression in many studies. However, the molecular mechanisms underlying PCa progression remain unclear.

MATERIALS AND METHODS:

We investigated the lncRNA transcriptome using publicly available RNA-sequencing data to identify prostate-specific lncRNAs. Then, the chromatin immunoprecipitation (ChIP) assay identified lncRNA with a direct binding to androgen receptor (AR), hereafter denoted as PSLNR. Quantitative real-time polymerase chain reaction analysis and Western blot analysis were performed to detect the expression of p53 signaling-related genes after overexpression PSLNR. The effects of overexpression of PSLNR on cell proliferation, cell cycle, and cell apoptosis were assessed by using CCK-8 and flow cytometric analysis. We then detected the expression of PSLNR in tissues.

RESULT:

We reported a novel androgen-reduced prostate-specific lncRNA, PSLNR, that inhibited PCa progression via the p53-dependent pathway. By analyzing the NOCODE data set, we reported that PSLNR was specifically expressed in the prostate, suggesting the potential of PSLNR as a biomarker for PCa treatment. The AR pathway was also confirmed to be an upstream regulation signaling pathway of PSLNR by transcriptionally regulating its expression in androgen-dependent PCa cells. PSLNR also significantly inhibited PCa proliferation by inducing cell apoptosis in a p53-dependent manner. Thus, PSLNR may be a candidate diagnosis and therapeutic target for PCa.

CONCLUSIONS:

Our study revealed for the first time a novel androgen-reduced prostate-specific lncRNA, PSLNR, which inhibited PCa progression via the p53-dependent pathway, suggesting that PSLNR may be a candidate diagnosis and therapeutic target for PCa.

KEYWORDS:

TP53; androgen receptor; diagnosis target; prostate cancer; prostate-specific

PMID:
31269242
DOI:
10.1002/pros.23840

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