The long non-coding RNA PCGEM1 is regulated by androgen receptor activity in vivo

Abstract

BackgroundLong non-coding RNAs (lncRNAs) can orchestrate oncogenic or tumor-suppressive functions in cancer biology. Accordingly, PCGEM1 and PRNCR1 were implicated in progression of prostate cancer (PCa) as transcriptional co-regulators of the androgen receptor (AR). However, these findings were recently refuted asserting that neither gene physically binds to the AR. Despite evidence for differing AR transcriptional programs in vivo and in vitro, studies investigating AR-regulation of these genes hitherto have only been conducted in vitro. Here, we further examine the relevance of PCGEM1 and PRNCR1 in PCa, and their relationship with AR signaling, using patient-derived xenograft models.FindingsRNA sequencing of two distinct androgen-dependent models shows PCGEM1 to be considerably expressed, while PRNCR1 showed scant basal expression. PCGEM1 was sharply down-regulated following castration and up-regulated upon AR activation in vivo. However, we found no parallel evidence following AR stimulation in vitro. A PCGEM1-associated gene expression signature (PES) was significantly repressed in response to androgen ablation therapy and in hormone-refractory versus hormone-naïve PCa patients. Furthermore, we found PCGEM1 was uniformly distributed in PCa cell nucleus and cytoplasm which remained unaltered upon AR transcriptional activation. PCGEM1 was up-regulated in primary PCa but not in metastasized PCa. Accordingly, the PES was significantly down-regulated in advanced and higher grade PCa patients from multiple independent studies.ConclusionOur results demonstrate PCGEM1 as an in vivo androgen-regulated transcript with potential nuclear and/or cytoplasmic function(s). Importantly, the clinical expression profile of PCGEM1 implicates it in the early stages of PCa warranting further research in this direction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0314-4) contains supplementary material, which is available to authorized users.

Long noncoding RNA LINC01296 is associated with poor prognosis in prostate cancer and promotes cancer-cell proliferation and metastasis

“…EMT is an important step in metastasis, during which epithelial cells are transformed into mesenchymal cells under specific physiological and pathological conditions 30,31. MMP9 is frequently observed in prostate cancer progression,32,33 and the upregulated expression of MMP9 is usually correlated with the occurrence of metastasis or local progression of cancer 16. Studies have found that lncRNA promotes cancer metastasis by regulating the EMT process 34,35.…”

Integrated analysis of the prostate cancer small‐nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression

“…For the highly migrating DU145 cell line, pictures were taken till full “healing” of the NC‐treated cells (20 h). Cell fractionation and dihydrotestosterone (DHT) treatment of LNCaP cells have been previously described (Parolia et al., 2015).…”

Long non-coding RNA PCGEM1 as a biomarker for prostate cancer

“…Although the involvement of PCGEM1 in PC was widely reported, the role of PCGEM1 in PC is still controversial. For example, androgen deprivation is able to induce PCGEM1 and causes its accumulation in nuclear speckles 17 , while this was not the case in another study which revealed that PCGEM1 was stimulated by androgen and downregulated by castration in xenograft models 16 . Similarly, PCGEM1 along with PRNCR1 can impact AR signalling through interaction with AR to promote castration resistance 18 , however, this is not supported by a comprehensive analysis of RNA-sequencing data 19 .…”

“…PCGEM1 overexpression in LNCaP cells results in delayed induction of p53 and p21 induced by doxorubicin, which could therefore inhibit cell apoptosis 15 . Besides, PCGEM1 is an in vivo androgenregulated transcript with potential nuclear and/or cytoplasmic function 16 . Although the involvement of PCGEM1 in PC was widely reported, the role of PCGEM1 in PC is still controversial.…”