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 therapy. 2024 Aug 15 [Epub ahead of print]
Annika Kohvakka, Mina Sattari, Janika Nättinen, Ulla Aapola, Pavlína Gregorová, Teuvo L J Tammela, Hannu Uusitalo, L Peter Sarin, Tapio Visakorpi, Leena Latonen
Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, 33520, Tampere, Finland., Eye and Vision Research Group, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland., RNAcious Laboratory, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland., Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, 33520, Tampere, Finland. ., Institute of Biomedicine, University of Eastern Finland, 70211, Kuopio, Finland. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39147845