title: Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer.
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.
authors: Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada.
authors: Francesco
authors: F
authors: Crea
authors: Akira
authors: A
authors: Watahiki
authors: Luca
authors: L
authors: Quagliata
authors: Hui
authors: H
authors: Xue
authors: Larissa
authors: L
authors: Pikor
authors: Abhijit
authors: A
authors: Parolia
authors: Yuwei
authors: Y
authors: Wang
authors: Dong
authors: D
authors: Lin
authors: Wan L
authors: WL
authors: Lam
authors: William L
authors: WL
authors: Farrar
authors: Takao
authors: T
authors: Isogai
authors: Rudolf
authors: R
authors: Morant
authors: Serenella
authors: S
authors: Castori-Eppenberger
authors: Kim N
authors: KN
authors: Chi
authors: Yuzhuo
authors: Y
authors: Wang
authors: Cheryl D
authors: CD
authors: Helgason
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D011944:Receptors, Androgen