Numerous noncoding transcripts have been reported to correlate with cancer development and progression. Nevertheless, there remains a paucity of long noncoding RNAs (lncRNA) with well-elucidated functional roles. Here, we leverage the International Cancer Genome Consortium-Early Onset Prostate Cancer transcriptome and identify the previously uncharacterized lncRNA LINC00920 to be upregulated in prostate tumors. Phenotypic characterization of LINC00920 revealed its positive impact on cellular proliferation, colony formation, and migration. We demonstrate that LINC00920 transcription is directly activated by ERG, an oncogenic transcription factor overexpressed in 50% of prostate cancers. Chromatin isolation by RNA purification-mass spectrometry revealed the interaction of LINC00920 with the 14-3-3ϵ protein, leading to enhanced sequestration of tumor suppressive FOXO1. Altogether, our results provide a rationale on how ERG overexpression, partly by driving LINC00920 transcription, could confer survival advantage to prostate cancer cells and potentially prime PTEN-intact prostate cells for cellular transformation through FOXO inactivation. Implications: The study describes a novel lncRNA-mediated mechanism of regulating the FOXO signaling pathway and provides additional insight into the role of ERG in prostate cancer cells.

中文翻译：

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ERG 调节的 LINC00920 通过 14-3-3ε-FOXO 通路促进前列腺癌细胞存活

据报道，许多非编码转录本与癌症的发展和进展相关。尽管如此，仍然缺乏具有充分阐明的功能作用的长链非编码 RNA (lncRNA)。在这里，我们利用国际癌症基因组联盟-早发性前列腺癌转录组并确定了以前未表征的 lncRNA LINC00920 在前列腺肿瘤中上调。LINC00920 的表型特征揭示了其对细胞增殖、集落形成和迁移的积极影响。我们证明 LINC00920 转录被 ERG 直接激活，ERG 是一种在 50% 的前列腺癌中过度表达的致癌转录因子。通过 RNA 纯化-质谱法分离染色质揭示了 LINC00920 与 14-3-3ϵ 蛋白的相互作用，导致增强的肿瘤抑制性 FOXO1 的隔离。总而言之，我们的结果提供了一个基本原理，说明 ERG 过表达（部分通过驱动 LINC00920 转录）可以赋予前列腺癌细胞生存优势，并可能通过 FOXO 灭活为 PTEN 完整的前列腺细胞进行细胞转化。意义：该研究描述了一种新的 lncRNA 介导的调节 FOXO 信号通路的机制，并提供了对 ERG 在前列腺癌细胞中的作用的额外见解。