The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor.

Emerging evidences implicate long noncoding RNAs (lncRNAs) are deregulated in cancer development. The purpose of the current study is to investigate the role of new lncRNA, named PlncRNA-1, in prostate cancer (CaP) pathogenesis. In this study, real-time q-PCR was used to demonstrate the expression of PlncRNA-1 in 16 pairs CaP tissues and matched normal tissues, 14 pairs CaP tissues and BPH tissues, 4 CaP cell lines, including LNCaP, LNCaP-AI, PC3, and C4-2, and 2 normal prostate epithelial cell lines RWPE-1 and PWR-1E. After PlncRNA-1 was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, cell proliferation and apoptosis were assessed using CCK-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). After PlncRNA-1 and AR was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, real-time q-PCR and Western blotting were used to measure reciprocal regulation of PlncRNA-1 and AR. We showed that expression PlncRNA-1, was significantly higher in CaP cells relative to normal prostate epithelial cells, as well as higher in human CaPs compared with normal tissues and benign prostatic hyperplasia (BPH). Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI. Mechanistically, PlncRNA-1 suppression by siRNA resulted in a decrease of androgen receptor (AR) mRNA, protein and AR downstream target. Of note, blockade of AR signaling with siRNA also resulted in a suppression of PlncRNA-1 expression in CaP cell lines. Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target.

Cui Z ，Ren S ，Lu J ，Wang F ，Xu W ，Sun Y ，Wei M ，Chen J ，Gao X ，Xu C ，Mao JH ，Sun Y ... -  《-》

Androgen receptor as a regulator of ZEB2 expression and its implications in epithelial-to-mesenchymal transition in prostate cancer.

Jacob S ，Nayak S ，Fernandes G ，Barai RS ，Menon S ，Chaudhari UK ，Kholkute SD ，Sachdeva G ... -  《-》

Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer.

Jin Y ，Cui Z ，Li X ，Jin X ，Peng J ... -  《Oncotarget》

A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression.

We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa.

Fang Z ，Xu C ，Li Y ，Cai X ，Ren S ，Liu H ，Wang Y ，Wang F ，Chen R ，Qu M ，Wang Y ，Zhu Y ，Zhang W ，Shi X ，Yao J ，Gao X ，Hou J ，Xu C ，Sun Y ... -  《-》

Growth hormone (GH) receptors in prostate cancer: gene expression in human tissues and cell lines and characterization, GH signaling and androgen receptor regulation in LNCaP cells.

Weiss-Messer E ，Merom O ，Adi A ，Karry R ，Bidosee M ，Ber R ，Kaploun A ，Stein A ，Barkey RJ ... -  《MOLECULAR AND CELLULAR ENDOCRINOLOGY》