Long non-coding RNAs (lncRNAs) participate in the development and progression of prostate cancer (PCa). We aimd to identify a novel lncRNA, named lncRNA activated in metastatic PCa (lncAMPC), and investigate its mechanisms and clinical significance in PCa. First, the biological capacity of lncAMPC in PCa was demonstrated both in vitro and in vivo. The lncAMPC was overexpressed in tumor tissue and urine of metastatic PCa patients and promoted PCa tumorigenesis and metastasis. Then, a mechanism study was conducted to determine how the lncAMPC-activated pathway contributed to PCa metastasis and immunosuppression. In the cytoplasm, lncAMPC upregulated LIF expression by sponging miR-637 and inhibiting its activity. In the nucleus, lncAMPC enhanced LIFR transcription by decoying histone H1.2 away from the upstream sequence of the LIFR gene. The lncAMPC-activated LIF/LIFR expressions stimulated the Jak1-STAT3 pathway to simultaneously maintain programmed death-ligand 1 (PD-L1) protein stability and promote metastasis-associated gene expression. Finally, the prognostic value of the expression of lncAMPC and its downstream genes in PCa patients was evaluated. High LIF/LIFR levels indicated shorter biochemical recurrence-free survival among patients who underwent radical prostatectomy. Therefore, the lncAMPC/LIF/LIFR axis plays a critical role in PCa metastasis and immunosuppression and may serve as a prognostic biomarker and potential therapeutic target.

长链非编码 RNA (lncRNA) 参与前列腺癌 (PCa) 的发生和进展。我们旨在鉴定一种新的 lncRNA，命名为在转移性 PCa 中激活的 lncRNA (lncAMPC)，并研究其在 PCa 中的机制和临床意义。首先，lncAMPC 在 PCa 中的生物学能力在体外和体内都得到了证明. lncAMPC在转移性PCa患者的肿瘤组织和尿液中过度表达，促进了PCa的肿瘤发生和转移。然后，进行了机制研究以确定 lncAMPC 激活的途径如何促进 PCa 转移和免疫抑制。在细胞质中，lncAMPC 通过吸附 miR-637 并抑制其活性来上调 LIF 表达。在细胞核中，lncAMPC 通过从 LIFR 基因的上游序列诱骗组蛋白 H1.2 来增强 LIFR 转录。lncAMPC 激活的 LIF/LIFR 表达刺激 Jak1-STAT3 通路同时维持程序性死亡配体 1 (PD-L1) 蛋白稳定性并促进转移相关基因表达。最后，评估了 lncAMPC 及其下游基因在 PCa 患者中表达的预后价值。高 LIF/LIFR 水平表明接受根治性前列腺切除术的患者的生化无复发生存期较短。因此，lncAMPC/LIF/LIFR 轴在 PCa 转移和免疫抑制中起着关键作用，可作为预后生物标志物和潜在的治疗靶点。