尽管已发现数百种与癌症相关的长非编码 RNA (lncRNA)，但它们在癌细胞中的功能作用在很大程度上仍然是个谜。越来越多的 lncRNA 被认为在细胞质中发挥作用，例如作为翻译调节剂。在这里，我们研究了 EPCART 的详细分子身份和功能作用，EPCART 是我们之前发现的一种 lncRNA，是前列腺癌 (PCa) 的潜在癌基因。首先，我们询问了 EPCART 的转录结构，然后使用计算机方法确认 EPCART 是非肽编码 lncRNA。 EPCART 敲除细胞中差异表达的蛋白质编码基因的通路分析表明 EPCART 调节 PCa 细胞的翻译机制。 EPCART 也主要位于细胞质和翻译位点。通过对 EPCART 敲除细胞进行定量蛋白质组分析，我们发现 PDCD4（一种蛋白质翻译抑制剂）会因 EPCART 减少而增加。进一步的研究表明，EPCART 沉默对翻译的抑制作用是通过减少 AKT 激活和抑制 mTORC1 通路介导的。总之，我们的研究结果确定 EPCART 是一种翻译相关的 lncRNA，通过调节 PCa 细胞中的 PI3K/AKT/mTORC1 通路发挥作用。此外，我们还提供了与 EPCART 有关的 PDCD4 在 PCa 肿瘤中的预后潜力的证据。© 2024。作者。

While hundreds of cancer-associated long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still largely a mystery. An increasing number of lncRNAs are recognized to function in the cytoplasm, e.g., as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in prostate cancer (PCa). First, we interrogated the transcript structure of EPCART and then confirmed EPCART to be a non-peptide-coding lncRNA using in silico methods. Pathway analysis of differentially expressed protein-coding genes in EPCART knockout cells implied that EPCART modulates the translational machinery of PCa cells. EPCART was also largely located in the cytoplasm and at the sites of translation. With quantitative proteome analysis on EPCART knockout cells we discovered PDCD4, an inhibitor of protein translation, to be increased by EPCART reduction. Further studies indicated that the inhibitory effect of EPCART silencing on translation was mediated by reduced activation of AKT and inhibition of the mTORC1 pathway. Together, our findings identify EPCART as a translation-associated lncRNA that functions via modulation of the PI3K/AKT/mTORC1 pathway in PCa cells. Furthermore, we provide evidence for the prognostic potential of PDCD4 in PCa tumors in connection with EPCART.© 2024. The Author(s).