Long Non-Coding RNA PCAT-NE1 Activates Autophagy via miR-6889-3p-Regulated VPS13A to Induce Neuroendocrine Differentiation

Neuroendocrine prostate cancer (NEPC) is a drug-resistant lethal variant of castration-resistant prostate cancer (CRPC) that is becoming increasingly common following the application of second-generation anti-hormonal therapy. However, the underlying mechanisms of neuroendocrine differentiation (NED) of prostate cancer (PCa) remain unclear. Long non-coding RNAs (lncRNAs) have recently been implicated in promoting lineage plasticity, a biological process that contributes to the acquisition of neuroendocrine (NE) characteristics. Here, we identified a novel lncRNA LINC01801 that is overexpressed in NEPC and which contributes to NED of PCa. We designated this lncRNA prostate cancer associated transcript-neuroendocrine 1 (PCAT-NE1). PCAT-NE1 acts as a competing endogenous RNA (ceRNA) that sponge hsa-miR-6889-3p, leading to the up-regulation of autophagy-related gene VPS13A and autophagy activation. Forced expression of miR-6889-3p and knockdown of VPS13A both inhibit NED induced by PCAT-NE1 overexpression. This study demonstrates that a novel PCa-associated lncRNA PCAT-NE1 promotes NED of PCa by decreasing the inhibitory effect of miR-6889-3p on autophagy signaling. Therefore, PCAT-NE1-miR-6889-3p-VPS13A axis may provide a new prognostic biomarker and therapeutic strategy for treatment-induced NEPC.