Novel lncRNA <i>LINC00844</i> Regulates Prostate Cancer Cell Migration and Invasion through AR Signaling

Abstract

The human genome is mostly transcribed, yielding a rich repository of noncoding transcripts that are involved in a myriad of biological processes including cancer. However, how many noncoding transcripts such as long noncoding RNAs (lncRNA) function in cancer is still unclear. This study identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, <i>LINC00844</i> was demonstrated to be a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)-dependent prostate cancer cells. The expression of <i>LINC00844</i> is higher in normal prostate compared with malignant and metastatic prostate cancer clinical specimens, and patients with low expression had a poor prognosis and significantly increased biochemical recurrence, suggesting <i>LINC00844</i> functions in suppressing tumor progression and metastasis. Indeed, <i>in vitro</i> loss-of-function studies revealed that <i>LINC00844</i> prevents prostate cancer cell migration and invasion. Moreover, findings from gene expression profiling analysis indicated that <i>LINC00844</i> functions in <i>trans</i>, affecting global androgen-regulated gene transcription. Mechanistic evidence reveals that <i>LINC00844</i> is important in facilitating AR binding to the chromatin. Finally, <i>LINC00844</i> mediates its phenotypic effects in part by activating the expression of <i>NDRG1</i>, a crucial cancer metastasis suppressor. Collectively, <i>LINC00844</i> is a novel coregulator of AR that plays a central role in the androgen transcriptional network and the development and progression of prostate cancer. IMPLICATIONS: This study highlights the function of the lncRNA, <i>LINC00844</i>, in regulating global AR-regulated genes in prostate cancer by modulating AR binding to chromatin.