文章：

长链非编码RNA EPCART通过PI3K/AKT/mTOR通路及PDCD4调控前列腺癌中的翻译过程

Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer 

原文发布日期：2024-08-15 

英文摘要：

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. 

摘要翻译：

尽管已有数百种癌症相关长链非编码RNA（lncRNA）被发现，但它们在癌细胞中的功能作用仍 largely 是个未解之谜。越来越多lncRNA被证实主要在细胞质中发挥作用，例如作为翻译调节因子。本研究深入探讨了EPCART（一种我们先前发现的前列腺癌潜在致癌基因）的详细分子特性与功能作用。首先我们解析了EPCART的转录本结构，并通过生物信息学方法确认其属于非肽编码lncRNA。对EPCART基因敲除细胞中差异表达蛋白编码基因的通路分析表明，EPCART可调节前列腺癌细胞的翻译机制。EPCART主要定位于细胞质及翻译位点。通过定量蛋白质组学分析发现，在EPCART敲除细胞中蛋白质翻译抑制因子PDCD4的表达量上升。进一步研究表明，EPCART沉默通过降低AKT活化度和抑制mTORC1通路来介导翻译抑制效应。我们的研究共同证实：EPCART是一种通过调节PI3K/AKT/mTORC1通路在前列腺癌细胞中发挥作用的翻译相关lncRNA。此外，我们还为PDCD4在前列腺肿瘤中与EPCART相关的预后潜力提供了证据。

原文链接：

Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer