Electronic Resource
METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
| العنوان: | METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer |
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| المؤلفون: | Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Junta de Castilla y León, Universidad de Salamanca, Banco Santander, Asociación Española Contra el Cáncer, Fundación CRIS contra el Cáncer, Fundación la Caixa, European Research Council, European Commission, García-Vílchez, Raquel, Añazco-Guenkova, Ana M., Dietmann, Sabine, López, Judith, Morón-Calvente, Virginia, D'Ambrosi, Silvia, Nombela, Paz, Zamacola, Kepa, Mendizábal, Isabel, García-Longarte, Saioa, Zabala-Letona, Amaia, Astobiza, Ianire, Fernández, Sonia, Paniagua, Alejandro, Miguel-López, Borja, Marchand, Virginie, Alonso-López, Diego, Merkel, Angelika, García-Tuñón, Ignacio, Ugalde-Olano, Aitziber, Loizaga-Iriarte, Ana, Lacasa-Viscasillas, Isabel, Unda, Miguel, Azkargorta, Mikel, Elortza, Félix, Bárcena, Laura, Gonzalez-Lopez, Monika, Aransay, Ana M., Di Domenico, Tomás, Sánchez-Martín, Manuel A., De Las Rivas, Javier, Guil, Sònia, Motorin, Yuri, Helm, Mark, Pandolfi, Pier Paolo, Carracedo, Arkaitz, Blanco, Sandra |
| بيانات النشر: | BioMed Central 2023-07-29 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7G tRNA methylation in cancer cell translation control and tumour biology. |
| مصطلحات الفهرس: | Epitranscriptome, RNA modifications, Prostate cancer, 7-methylguanosine, tRNA fragments, Tumour microenvironment (TME), Interferon, Immune checkpoint blockade, artículo |
| URL: | Molecular cancer Publisher's version Sí info:eu-repo/grantAgreement/MINECO//SAF2016-78667-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111692RB-I00/ES/PAPEL DEL EPITRANSCRIPTOMA Y SU IMPLICACION EN LA METASTASIS Y LA RESPUESTA INMUNE EN CANCER info:eu-repo/grantAgreement/MINECO//RYC-2014-16550/ES/RYC-2014-16550 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108787RB-I00/ES/ESTUDIO DE REGULADORES DE LA PROGRESION DEL CANCER DE PROSTATA EN LA INTERFASE DE METABOLISMO Y SEÑALIZACION CELULAR info:eu-repo/grantAgreement/AEI//RED2018-102769-T |
| الاتاحة: | Open access content. Open access content https://creativecommons.org/licenses/by/4.0 openAccess |
| ملاحظة: | English |
| Other Numbers: | CTK oai:digital.csic.es:10261/347759 Molecular Cancer 22: 119 (2023) 10.1186/s12943-023-01809-8 1476-4598 37516825 2-s2.0-85165971512 1431962737 |
| المصدر المساهم: | CSIC From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1431962737 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |