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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Parolia, Abhijit Crea, Francesco Xue, Hui Wang, Yuwei Mo, Fan Ramnarine, Varune Rohan Liu, Hui Hsuan Lin, Dong Saidy, Nur Ridzwan Nur Clermont, Pier-Luc Cheng, Hongwei Collins, Colin Wang, Yuzhuo Helgason, Cheryl D |
| Abstract | Background Long 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. Findings RNA 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. Conclusion Our 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. |
| Related Links | https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-015-0314-4.pdf |
| Ending Page | 7 |
| Page Count | 7 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14764598 |
| DOI | 10.1186/s12943-015-0314-4 |
| Journal | Molecular Cancer |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-02-21 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology PCGEM1 PRNCR1 PCAT18 Long non-coding RNAs lncRNAs Androgen receptor AR regulation Sub-cellular localization Prostate cancer |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology Molecular Medicine Cancer Research |
| Journal Impact Factor | 27.7/2023 |
| 5-Year Journal Impact Factor | 31.3/2023 |
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