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Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer

Crea, Francesco; Watahiki, Akira; Quagliata, Luca; Xue, Hui; Pikor, Larissa; Parolia, Abhijit; Wang, Yuwei; Lin, Dong; Lam, Wan L.; Farrar, William L.; Isogai, Takao; Morant, Rudolf; Castori-Eppenberger, Serenella; Chi, Kim N.; Wang, Yuzhuo and Helgason, Cheryl D. (2014). Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget, 5(3) pp. 764–774.

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DOI (Digital Object Identifier) Link: https://doi.org/10.18632/oncotarget.1769
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Abstract

Metastatic prostate cancer (PCa) is still an incurable disease. Long non-coding RNAs (lncRNAs) may be an overlooked source of cancer biomarkers and therapeutic targets. We therefore performed RNA sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The most highly up-regulated transcript was LOC728606, a lncRNA now designated PCAT18. PCAT18 is specifically expressed in the prostate compared to 11 other normal tissues (p<0.05) and up-regulated in PCa compared to 15 other neoplasms (p<0.001). Cancer-specific up-regulation of PCAT18 was confirmed on an independent dataset of PCa and benign prostatic hyperplasia samples (p<0.001). PCAT18 was detectable in plasma samples and increased incrementally from healthy individuals to those with localized and metastatic PCa (p<0.01). We identified a PCAT18-associated expression signature (PES), which is highly PCa-specific and activated in metastatic vs. primary PCa samples (p<1E-4, odds ratio>2). The PES was significantly associated with androgen receptor (AR) signalling. Accordingly, AR activation dramatically up-regulated PCAT18 expression in vitro and in vivo. PCAT18 silencing significantly (p<0.001) inhibited PCa cell proliferation and triggered caspase 3/7 activation, with no effect on non-neoplastic cells. PCAT18 silencing also inhibited PCa cell migration (p<0.01) and invasion (p<0.01). These results position PCAT18 as a potential therapeutic target and biomarker for metastatic PCa.

Item Type: Journal Item
Copyright Holders: 2014 The Authors
ISSN: 1949-2553
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 45787
Depositing User: Francesco Crea
Date Deposited: 14 Apr 2016 09:55
Last Modified: 08 Dec 2018 07:09
URI: http://oro.open.ac.uk/id/eprint/45787
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