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Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2024 Oct; Vol. 31 (10), pp. 1536-1546. Date of Electronic Publication: 2024 Aug 15. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Male
Signal Transduction
Cell Line, Tumor
Protein Biosynthesis
Gene Expression Regulation, Neoplastic
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Prostatic Neoplasms genetics
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
TOR Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Phosphatidylinositol 3-Kinases metabolism
RNA-Binding Proteins metabolism
RNA-Binding Proteins genetics
Apoptosis Regulatory Proteins genetics
Apoptosis Regulatory Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 39147845
- Full Text :
- https://doi.org/10.1038/s41417-024-00822-3