biostudies-literatureKohvakka ASyöpäsäätiöNovo Nordisk Fonden (Novo Nordisk Foundation)Elsemay Björn FundSigrid Juséliuksen SäätiöSuomen Akatemia | Terveyden Tutkimuksen ToimikuntaEC | Horizon 2020 Framework ProgrammeNovo Nordisk FondenEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)Suomen Akatemia | Terveyden Tutkimuksen Toimikunta (Research Council for Health)1536-1546https://www.ebi.ac.uk/biostudies/studies/S-EPMC11489079biostudies-literatureUnknown31(10)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.Cancer gene therapyLong noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer.PMC11489079721746NNF19OC0054454317755357490Gregorova PSattari MUusitalo HKohvakka ATammela TLJVisakorpi TSarin LPLatonen LNattinen JAapola UfalseLong noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer.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.2024-01-01T00:00:00Z2024 Oct2025-04-04T14:37:36.026Z2025-04-04T14:37:36.026ZS-EPMC114890793914784510.1038/s41417-024-00822-3