1. Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma.
- Author
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Gugnoni M, Lorenzini E, Torricelli F, Donati B, Manicardi V, Vitale E, Muccioli S, Piana S, Lococo F, Zamponi R, Gandellini P, and Ciarrocchi A
- Subjects
- Humans, Cell Line, Tumor, Pleural Neoplasms genetics, Pleural Neoplasms pathology, Pleural Neoplasms metabolism, Ribosomes metabolism, Ribosomes genetics, Retrospective Studies, Prognosis, Cell Proliferation, Mesothelioma, Malignant genetics, Mesothelioma, Malignant pathology, Mesothelioma, Malignant metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Protein Biosynthesis, Eukaryotic Initiation Factor-4G genetics, Eukaryotic Initiation Factor-4G metabolism, Mesothelioma genetics, Mesothelioma pathology, Mesothelioma metabolism, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Lung Neoplasms genetics, Lung Neoplasms pathology, Lung Neoplasms metabolism, Gene Expression Regulation, Neoplastic
- Abstract
Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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