Abstract
Long noncoding RNAs (IncRNAs) are increasingly implicated in cancer biology, contributing to essential cancer cell functions such as proliferation, invasion, and metastasis. In prostate cancer, several lncRNAs have been nominated as critical actors in disease pathogenesis. Among these, expression of PCGEM1 and PRNCR1 has been identified as a possible component in disease progression through the coordination of androgen receptor (AR) signaling (Yang et al., Nature 2013, see ref. [1]). However, concerns regarding the robustness of these findings have been suggested. Here, we sought to evaluate whether PCGEM1 and PRNCR1 are associated with prostate cancer. Through a comprehensive analysis of RNA-sequencing data (RNA-seq), we find evidence that PCGEM1 but not PRNCR1 is associated with prostate cancer. We employ a large cohort of >230 high-risk prostate cancer patients with long-term outcomes data to show that, in contrast to prior reports, neither gene is associated with poor patient outcomes. We further observe no evidence that PCGEM1 nor PRNCR1 interact with AR, and neither gene is a component of AR signaling. Thus, we conclusively demonstrate that PCGEM1 and PRNCR1 are not prognostic lncRNAs in prostate cancer and we refute suggestions that these lncRNAs interact in AR signaling.
Highlights
Long noncoding RNAs have emerged as a critical element in cell biology, contributing to a wide variety of cellular behaviors and functions [2]
Two Long noncoding RNAs (lncRNAs), PCGEM1 and PRNCR1, have been suggested in prostate cancer to act as mediators of castration-resistance disease by binding, in a direct and sequential fashion, to the androgen receptor (AR), causing ligand-independent activation of its gene expression programs [1]
While PCGEM1 has been observed in prostate cancer previously [6, 10], PRNCR1 is a poorly characterized transcript, and we were concerned that PRNCR1 had not been nominated by previous global profiling studies of prostate cancers [7, 11,12,13,14]
Summary
Long noncoding RNAs (lncRNAs) have emerged as a critical element in cell biology, contributing to a wide variety of cellular behaviors and functions [2]. DHT-stimulated cells demonstrated no induction in PCGEM1 or PRNCR1 expression (Supplementary Fig. 7) These results imply that PCGEM1 and PRNCR1 are not AR-interacting lncRNAs. earlier data propose that PCGEM1 and PRNCR1 interact with AR via specific post-translational modifications (PTMs), K349 methylation (K349Me) for PCGEM1 and K631/K634 acetylation (K631Ac/K634Ac) for PRNCR1 [1]. To examine this discrepancy further, we re-analyzed prior AR MS data (found in [1]) This MS dataset was obtained with a trypsin digestion to prepare samples for MS, we found no fully tryptic peptides supporting the nomination of K349Me, K631Ac, or K634Ac (Supplementary Fig. 8). While our results challenge the notion that PCGEM1 and PRNCR1 play a causal role in prostate cancer, we regard lncRNAs as an emerging field of study in cancer [3, 6, 20, 21] and we are encouraged by the interest in lncRNAs in prostate cancer
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