Endocrine Abstracts (2016) 42 P4 | DOI: 10.1530/endoabs.42.P4

Expression of a novel androgen-regulated long noncoding RNA correlates with progression-free survival in prostate cancer patients

Annika Kohvakka, Kati Kivinummi, Ville Kytölä, Antti Ylipää, Matti Annala, Alfonso Urbanucci, Matti Nykter & Tapio Visakorpi

Prostate Cancer Research Cancer, BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.

Prostate cancer (PC) is the second most frequently diagnosed cancer in men worldwide. 10–20% of the PC patients develop castration-resistant prostate cancer (CRPC) that has no curative therapies. There are also no effective prognostic markers to predict emergence of CRPCs. Long noncoding RNAs (lncRNAs) are a recently found group of RNAs that are not translated into proteins. Many of them are found to be differentially expressed in cancer, and shown to have a regulative role in tumorigenesis and tumor development. In addition, some lncRNAs have been associated with cancer progression and/or survival, making them potentially interesting as prognostic markers. Previously, we performed RNA sequencing of 28 hormonally untreated PC, 13 CRPC and 12 non-cancerous, benign prostatic hyperplasia tissue samples, out of which 145 novel PC-associated lncRNAs (PCATs) were discovered. Subsequently, the expression of 39 PCATs were analyzed in 87 samples from prostatectomy-treated PCs by qRT-PCR on Fluidigm Biomark HD, and the results were associated with clinical data. Some of the PCATs had a significant correlation with progression-free survival. One of these PCATs was also found to be a target of androgen receptor (AR) regulation. According to publicly available AR-ChIP-seq data, there is an AR binding site in the transcription start site of this novel PCAT in prostate cancer. Thus, we validated the AR binding by ChIP-qPCR in AR-expressing LNCaP and LuCaP cells. In addition, when AR was silenced by siRNAs, the expression of the PCAT was significantly diminished.

Presenting author: Annika Kohvakka, BioMediTech, University of Tampere, Biokatu 8, 33520, Tampere, Finland. Email: Annika.Kohvakka@staff.uta.fi.

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