Abstract
The lncRNA PCAT29 inhibits prostate cancer cell growth and migration and is suppressed by AR.
Major finding: The lncRNA PCAT29 inhibits prostate cancer cell growth and migration and is suppressed by AR.
Clinical relevance: Low PCAT29 expression may identify patients at higher risk for prostate cancer recurrence.
Impact: PCAT29 is a tumor-suppressive lncRNA of prognostic and therapeutic relevance in prostate cancer.
Long noncoding RNAs (lncRNA) comprise a large portion of the transcriptome and have been shown to contribute to tumor initiation and progression in various types of cancer, including prostate cancer. However, the role of most lncRNAs in tumorigenesis remains unknown. Malik and colleagues characterized prostate cancer–associated transcript 29 (PCAT29) as a 694bp lncRNA composed of six exons that is actively transcribed and differentially expressed in prostate cancer compared with normal tissue. PCAT29 expression was negatively regulated by the androgen receptor (AR), which bound directly to a putative enhancer region near the transcriptional start site of PCAT29 in response to stimulation with dihydrotestosterone, whereas castration therapy increased PCAT29 expression in a prostate cancer xenograft model. Intriguingly, depletion of PCAT29 enhanced the proliferation and migration of AR-expressing prostate cancer cells, whereas ectopic PCAT29 expression inhibited prostate cancer cell growth and migration, indicative of a tumor-suppressive role for this lncRNA. Consistent with this idea, overexpression of PCAT29 reduced prostate tumor growth and decreased liver metastasis in vivo in a chick chorioallantoic membrane assay. Furthermore, analysis of samples from 51 patients with localized hormone-sensitive prostate cancer revealed that low PCAT29 expression was associated with an increased rate of tumor recurrence, suggesting that PCAT29 may be a prognostic biomarker in prostate cancer. Although further work is necessary to define the mechanisms by which this lncRNA inhibits tumor growth and metastasis, these findings identify PCAT29 as an AR-regulated tumor-suppressive lncRNA in prostate cancer and provide evidence of the important role of lncRNAs in prostate tumorigenesis. In addition, these results suggest that reactivation of PCAT29 may contribute to the efficacy of androgen deprivation therapy and support additional studies of the prognostic and therapeutic relevance of lncRNAs in prostate cancer.
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