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3. Mitochondrial dysfunction promotes microbial composition that negatively impacts on ulcerative colitis development and progression

Author

Peña-Cearra, Ainize, Song, Deguang, Castelo, Janire, Palacios, Ainhoa, Lavín, Jose Luis, Azkargorta, Mikel, Elortza, Felix, Fuertes, Miguel, Pascual-Itoiz, Miguel Angel, Barriales, Diego, Martín-Ruiz, Itziar, Fullaondo, Asier, Aransay, Ana M., Rodríguez, Hector, Palm, Noah W., Anguita, Juan, and Abecia, Leticia

Published
2023
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4. METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Author

García-Vílchez, Raquel, Añazco-Guenkova, Ana M., Dietmann, Sabine, López, Judith, Morón-Calvente, Virginia, D’Ambrosi, Silvia, Nombela, Paz, Zamacola, Kepa, Mendizabal, 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, and Blanco, Sandra

Published
2023
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5. SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer

Author

Lachiondo-Ortega, Sofia, Rejano-Gordillo, Claudia M., Simon, Jorge, Lopitz-Otsoa, Fernando, C. Delgado, Teresa, Mazan-Mamczarz, Krystyna, Goikoetxea-Usandizaga, Naroa, Zapata-Pavas, L. Estefanía, García-del Río, Ana, Guerra, Pietro, Peña-Sanfélix, Patricia, Hermán-Sánchez, Natalia, Al-Abdulla, Ruba, Fernandez-Rodríguez, Carmen, Azkargorta, Mikel, Velázquez-Cruz, Alejandro, Guyon, Joris, Martín, César, Zalamea, Juan Diego, Egia-Mendikute, Leire, Sanz-Parra, Arantza, Serrano-Maciá, Marina, González-Recio, Irene, Gonzalez-Lopez, Monika, Martínez-Cruz, Luis Alfonso, Pontisso, Patrizia, Aransay, Ana M., Barrio, Rosa, Sutherland, James D., Abrescia, Nicola G.A., Elortza, Félix, Lujambio, Amaia, Banales, Jesus M., Luque, Raúl M., Gahete, Manuel D., Palazón, Asís, Avila, Matias A., G. Marin, Jose J., De, Supriyo, Daubon, Thomas, Díaz-Quintana, Antonio, Díaz-Moreno, Irene, Gorospe, Myriam, Rodríguez, Manuel S., and Martínez-Chantar, María Luz

Published
2024
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6. Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis

Author

Clària, Joan, Aguilar, Ferran, Lozano, Juan-José, Jiménez-Gracia, Laura, Nieto, Juan C., Romero-Grimaldo, Berta, Marcos-Fa, Xavi, Giarracco, Emma, Weiss, Emmanuel, Trebicka, Jonel, Hernàndez, Inmaculada, Fernandez, Javier, Casulleras, Mireia, López-Vicario, Cristina, Muldur, Sinan, Hopke, Alex, Vlagea, Alexandru, Aransay, Ana M., Marchese, Domenica, Bernardi, Mauro, Jalan, Rajiv, Angeli, Paolo, Magri, Giuliana, Cerutti, Andrea, Irimia, Daniel, Heyn, Holger, Arroyo, Vicente, and Moreau, Richard

Published
2024
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7. Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

Author

Capelo-Diz, Alba, Lachiondo-Ortega, Sofía, Fernández-Ramos, David, Cañas-Martín, Jorge, Goikoetxea-Usandizaga, Naroa, Serrano-Maciá, Marina, González-Rellan, Maria J., Mosca, Laura, Blazquez-Vicens, Joan, Tinahones-Ruano, Alberto, Fondevila, Marcos F., Buyan, Mason, Delgado, Teresa C., Gutierrez de Juan, Virginia, Ayuso-García, Paula, Sánchez-Rueda, Alejandro, Velasco-Avilés, Sergio, Fernández-Susavila, Héctor, Riobello-Suárez, Cristina, Dziechciarz, Bartlomiej, Montiel-Duarte, Cristina, Lopitz-Otsoa, Fernando, Bizkarguenaga, Maider, Bilbao-García, Jon, Bernardo-Seisdedos, Ganeko, Senra, Ana, Soriano-Navarro, Mario, Millet, Oscar, Díaz-Lagares, Ángel, Crujeiras, Ana B., Bao-Caamano, Aida, Cabrera, Diana, van Liempd, Sebastiaan, Tamayo-Caro, Miguel, Borzacchiello, Luigi, Gomez-Santos, Beatriz, Buqué, Xabier, Sáenz de Urturi, Diego, González-Romero, Francisco, Simon, Jorge, Rodríguez-Agudo, Rubén, Ruiz, Asier, Matute, Carlos, Beiroa, Daniel, Falcon-Perez, Juan M., Aspichueta, Patricia, Rodríguez-Cuesta, Juan, Porcelli, Marina, Pajares, María A., Ameneiro, Cristina, Fidalgo, Miguel, Aransay, Ana M., Lama-Díaz, Tomas, Blanco, Miguel G., López, Miguel, Villa-Bellosta, Ricardo, Müller, Timo D., Nogueiras, Rubén, Woodhoo, Ashwin, Martínez-Chantar, María Luz, and Varela-Rey, Marta

Published
2023
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8. Propionate and butyrate counteract renal damage and progression to chronic kidney disease

Author

Corte-Iglesias, Viviana, primary, Saiz, Maria Laura, additional, Andrade-Lopez, Ana Cristina, additional, Salazar, Nuria, additional, Bernet, Cristian Ruiz, additional, Martin-Martin, Cristina, additional, Borra, Jesús Martinez, additional, Lozano, Juan-Jose, additional, Aransay, Ana M, additional, Diaz-Corte, Carmen, additional, Lopez-Larrea, Carlos, additional, and Suarez-Alvarez, Beatriz, additional

Published
2024
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9. The transcriptional landscape of metastatic hormone-naive prostate cancer

Author

Martin-Martin, Natalia, primary, Garcia-Longarte, Saioa, additional, Corres-Mendizabal, Jon, additional, Lazcano, Uxue, additional, Astobiza, Ianire, additional, Bozal-Basterra, Laura, additional, Herranz, Nicolas, additional, van Splunder, Hielke, additional, Carlevaris, Onintza, additional, Pujana-Vaquerizo, Mikel, additional, Blasco, María Teresa, additional, Aransay, Ana M., additional, Rosino, Antonio, additional, Tudela, Julian, additional, Jimenez, Daniel, additional, Martinez, Alberto, additional, Salca, Andrei, additional, Santos-Martín, Aida, additional, Rey, Sofía, additional, Ugalde-Olano, Aitziber, additional, Gonzalo, David, additional, Graupera, Mariona, additional, Gomis, Roger R., additional, Mateo, Joaquin, additional, Unda, Miguel, additional, Gonzalez-Billalabeitia, Enrique, additional, Loizaga-Iriarte, Ana, additional, Mendizabal, Isabel, additional, and Carracedo, Arkaitz, additional

Published
2024
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11. MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis.

Author

Fernández-Ramos, David, Fernández-Tussy, Pablo, Lopitz-Otsoa, Fernando, Gutiérrez-de-Juan, Virginia, Navasa, Nicolás, Barbier-Torres, Lucía, Zubiete-Franco, Imanol, Simón, Jorge, Fernández, Agustín F, Arbelaiz, Ander, Aransay, Ana M, Lavín, José Luis, Beraza, Naiara, Perugorria, María J, Banales, Jesus M, Villa, Erica, Fraga, Mario F, Anguita, Juan, Avila, Matias A, Berasain, Carmen, Iruzibieta, Paula, Crespo, Javier, Lu, Shelly C, Varela-Rey, Marta, Mato, José M, Delgado, Teresa C, and Martínez-Chantar, María L

Subjects
Liver, Animals, Mice, Inbred C57BL, Humans, Mice, Carcinoma, Hepatocellular, Liver Cirrhosis, Fibrosis, MicroRNAs, Cell Proliferation, Male, Glycine N-Methyltransferase, Hepatic Stellate Cells, Inbred C57BL, Carcinoma, Hepatocellular, Biochemistry and Cell Biology, Oncology and Carcinogenesis
Abstract

Glycine N-methyltransferase (GNMT) is the most abundant methyltransferase in the liver and a master regulator of the transmethylation flux. GNMT downregulation leads to loss of liver function progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Moreover, GNMT deficiency aggravates cholestasis-induced fibrogenesis. To date, little is known about the mechanisms underlying downregulation of GNMT levels in hepatic fibrosis and cirrhosis. On this basis, microRNAs are epigenetic regulatory elements that play important roles in liver pathology. In this work, we aim to study the regulation of GNMT by microRNAs during liver fibrosis and cirrhosis. Luciferase assay on the 3'UTR-Gnmt was used to confirm in silico analysis showing that GNMT is potentially targeted by the microRNA miR-873-5p. Correlation between GNMT and miR-873-5p in human cholestasis and cirrhosis together with miR-873-5p inhibition in vivo in different mouse models of liver cholestasis and fibrosis [bile duct ligation and Mdr2 (Abcb4)-/- mouse] were then assessed. The analysis of liver tissue from cirrhotic and cholestatic patients, as well as from the animal models, showed that miR-873-5p inversely correlated with the expression of GNMT. Importantly, high circulating miR-873-5p was also detected in cholestastic and cirrhotic patients. Preclinical studies with anti-miR-873-5p treatment in bile duct ligation and Mdr2-/- mice recovered GNMT levels in association with ameliorated inflammation and fibrosis mainly by counteracting hepatocyte apoptosis and cholangiocyte proliferation. In conclusion, miR-873-5p emerges as a novel marker for liver fibrosis, cholestasis, and cirrhosis and therapeutic approaches based on anti-miR-873-5p may be effective treatments for liver fibrosis and cholestatic liver disease.

Published
2018

12. Role of Aramchol in steatohepatitis and fibrosis in mice.

Author

Iruarrizaga-Lejarreta, Marta, Varela-Rey, Marta, Fernández-Ramos, David, Martínez-Arranz, Ibon, Delgado, Teresa C, Simon, Jorge, Juan, Virginia Gutiérrez-de, delaCruz-Villar, Laura, Azkargorta, Mikel, Lavin, José L, Mayo, Rebeca, Van Liempd, Sebastiaan M, Aurrekoetxea, Igor, Buqué, Xabier, Cave, Donatella Delle, Peña, Arantza, Rodríguez-Cuesta, Juan, Aransay, Ana M, Elortza, Felix, Falcón-Pérez, Juan M, Aspichueta, Patricia, Hayardeny, Liat, Noureddin, Mazen, Sanyal, Arun J, Alonso, Cristina, Anguita, Juan, Martínez-Chantar, María Luz, Lu, Shelly C, and Mato, José M

Subjects
1-carbon metabolism, Lipid metabolism, Mouse model, S-adenosylmethionine
Abstract

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD) which sets the stage for further liver damage. The mechanism for the progression of NASH involves multiple parallel hits including oxidative stress, mitochondrial dysfunction, inflammation and others. Manipulation of any of these pathways may be an approach to prevent NASH development and progression. Aramchol (arachidyl-amido cholanoic acid) is presently in a phase IIb NASH study. The aim of this study was to investigate Aramchol's mechanism of action and its effect on fibrosis using the methionine- and choline-deficient (MCD) diet model of NASH. We collected liver and serum from mice fed a MCD diet containing 0.1% methionine (0.1MCD) for four weeks, which developed steatohepatitis and fibrosis, as well as mice receiving a control diet; the metabolomes and proteomes were determined. 0.1MCD fed mice were given Aramchol (5mg/kg/day for the last 2 weeks); liver samples were analyzed histologically. Aramchol administration reduced features of steatohepatitis and fibrosis in 0.1MCD fed mice. Aramchol downregulated stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in triglyceride biosynthesis whose loss enhances fatty acid β-oxidation. Aramchol increased the flux through the transsulfuration pathway, leading to a rise in glutathione (GSH) and GSH/GSSG ratio, the main cellular antioxidant that maintains intracellular redox status. Comparison of serum metabolomic pattern between 0.1MCD fed mice and NAFLD patients showed a substantial overlap. Conclusions:Aramchol treatment improved steatohepatitis and fibrosis by 1) decreasing SCD1, and 2) increasing the flux through the transsulfuration pathway maintaining cellular redox homeostasis. We also demonstrated that the 0.1MCD model resembles the metabolic phenotype observed in about 50% of NAFLD patients, which supports the potential use of Aramchol in NASH treatment.

Published
2017

13. Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination

Author

Ayuso-García, Paula, primary, Sánchez-Rueda, Alejandro, additional, Velasco-Avilés, Sergio, additional, Tamayo-Caro, Miguel, additional, Ferrer-Pinós, Aroa, additional, Huarte-Sebastian, Cecilia, additional, Alvarez, Vanesa, additional, Riobello, Cristina, additional, Jiménez-Vega, Selene, additional, Buendia, Izaskun, additional, Cañas-Martin, Jorge, additional, Fernández-Susavila, Héctor, additional, Aparicio-Rey, Adrián, additional, Esquinas-Román, Eva M., additional, Ponte, Carlos Rodríguez, additional, Guhl, Romane, additional, Laville, Nicolas, additional, Pérez-Andrés, Encarni, additional, Lavín, José L., additional, González-Lopez, Monika, additional, Cámara, Nuria Macías, additional, Aransay, Ana M., additional, Lozano, Juan José, additional, Sutherland, James D., additional, Barrio, Rosa, additional, Martinez-Chantar, María Luz, additional, Azkargorta, Mikel, additional, Elortza, Félix, additional, Soriano-Navarro, Mario, additional, Matute, Carlos, additional, Sánchez-Gómez, María Victoria, additional, Bayón-Cordero, Laura, additional, Pérez-Samartín, Alberto, additional, Bravo, Susana B., additional, Kurz, Thimo, additional, Lama-Díaz, Tomas, additional, Blanco, Miguel G., additional, Haddad, Saif, additional, Record, Christopher J., additional, van Hasselt, Peter M., additional, Reilly, Mary M., additional, Varela-Rey, Marta, additional, and Woodhoo, Ashwin, additional

Published
2024
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14. Global and single-nucleotide resolution detection of 7-methylguanosine in RNA

Author

D’Ambrosi, Silvia, primary, García-Vílchez, Raquel, additional, Kedra, Darek, additional, Vitali, Patrice, additional, Macias-Cámara, Nuria, additional, Bárcena, Laura, additional, Gonzalez-Lopez, Monika, additional, Aransay, Ana M., additional, Dietmann, Sabine, additional, Hurtado, Antonio, additional, and Blanco, Sandra, additional

Published
2024
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15. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis

Author

Alonso, Cristina, Fernández-Ramos, David, Varela-Rey, Marta, Martínez-Arranz, Ibon, Navasa, Nicolás, Van Liempd, Sebastiaan M, Trueba, José L Lavín, Mayo, Rebeca, Ilisso, Concetta P, de Juan, Virginia G, Iruarrizaga-Lejarreta, Marta, delaCruz-Villar, Laura, Mincholé, Itziar, Robinson, Aaron, Crespo, Javier, Martín-Duce, Antonio, Romero-Gómez, Manuel, Sann, Holger, Platon, Julian, Van Eyk, Jennifer, Aspichueta, Patricia, Noureddin, Mazen, Falcón-Pérez, Juan M, Anguita, Juan, Aransay, Ana M, Martínez-Chantar, María Luz, Lu, Shelly C, and Mato, José M

Subjects
Digestive Diseases, Chronic Liver Disease and Cirrhosis, Hepatitis, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Adult, Animals, Biomarkers, Ceramides, Diglycerides, Fatty Acids, Female, Humans, Lipid Metabolism, Male, Metabolome, Methionine Adenosyltransferase, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Non-alcoholic Fatty Liver Disease, S-Adenosylmethionine, Triglycerides, Mouse Model, 1-Carbon Metabolism, Prognostic, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsNonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis.MethodsWe collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis.ResultsLivers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice.ConclusionsIn an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be used to monitor disease progression and identify therapeutic targets for patients.

Published
2017

16. Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination

Author

Metabole ziekten patientenzorg, Child Health, Infection & Immunity, Ayuso-García, Paula, Sánchez-Rueda, Alejandro, Velasco-Avilés, Sergio, Tamayo-Caro, Miguel, Ferrer-Pinós, Aroa, Huarte-Sebastian, Cecilia, Alvarez, Vanesa, Riobello, Cristina, Jiménez-Vega, Selene, Buendia, Izaskun, Cañas-Martin, Jorge, Fernández-Susavila, Héctor, Aparicio-Rey, Adrián, Esquinas-Román, Eva M., Ponte, Carlos Rodríguez, Guhl, Romane, Laville, Nicolas, Pérez-Andrés, Encarni, Lavín, José L., González-Lopez, Monika, Cámara, Nuria Macías, Aransay, Ana M., Lozano, Juan José, Sutherland, James D., Barrio, Rosa, Martinez-Chantar, María Luz, Azkargorta, Mikel, Elortza, Félix, Soriano-Navarro, Mario, Matute, Carlos, Sánchez-Gómez, María Victoria, Bayón-Cordero, Laura, Pérez-Samartín, Alberto, Bravo, Susana B., Kurz, Thimo, Lama-Díaz, Tomas, Blanco, Miguel G., Haddad, Saif, Record, Christopher J., van Hasselt, Peter M., Reilly, Mary M., Varela-Rey, Marta, Woodhoo, Ashwin, Metabole ziekten patientenzorg, Child Health, Infection & Immunity, Ayuso-García, Paula, Sánchez-Rueda, Alejandro, Velasco-Avilés, Sergio, Tamayo-Caro, Miguel, Ferrer-Pinós, Aroa, Huarte-Sebastian, Cecilia, Alvarez, Vanesa, Riobello, Cristina, Jiménez-Vega, Selene, Buendia, Izaskun, Cañas-Martin, Jorge, Fernández-Susavila, Héctor, Aparicio-Rey, Adrián, Esquinas-Román, Eva M., Ponte, Carlos Rodríguez, Guhl, Romane, Laville, Nicolas, Pérez-Andrés, Encarni, Lavín, José L., González-Lopez, Monika, Cámara, Nuria Macías, Aransay, Ana M., Lozano, Juan José, Sutherland, James D., Barrio, Rosa, Martinez-Chantar, María Luz, Azkargorta, Mikel, Elortza, Félix, Soriano-Navarro, Mario, Matute, Carlos, Sánchez-Gómez, María Victoria, Bayón-Cordero, Laura, Pérez-Samartín, Alberto, Bravo, Susana B., Kurz, Thimo, Lama-Díaz, Tomas, Blanco, Miguel G., Haddad, Saif, Record, Christopher J., van Hasselt, Peter M., Reilly, Mary M., Varela-Rey, Marta, and Woodhoo, Ashwin

Published
2024

17. Global and single-nucleotide resolution detection of 7-methylguanosine in RNA

Author

Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Asociación Española Contra el Cáncer, Universidad de Salamanca, Fundación Memoria de D. Samuel Solorzano Barruso, Junta de Castilla y León, Consejo Superior de Investigaciones Científicas (España), D’Ambrosia, Silvia, García-Vílchez, Raquel, Kedrac, Darek, Vitalie, Patrice, Macias-Cámara, Nuria, Bárcena, Laura, Gonzalez-Lopez, Monika, Aransay, Ana M., Dietmann, Sabine, Hurtado, Antonio, Blanco, Sandra, Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Asociación Española Contra el Cáncer, Universidad de Salamanca, Fundación Memoria de D. Samuel Solorzano Barruso, Junta de Castilla y León, Consejo Superior de Investigaciones Científicas (España), D’Ambrosia, Silvia, García-Vílchez, Raquel, Kedrac, Darek, Vitalie, Patrice, Macias-Cámara, Nuria, Bárcena, Laura, Gonzalez-Lopez, Monika, Aransay, Ana M., Dietmann, Sabine, Hurtado, Antonio, and Blanco, Sandra

Abstract

RNA modifications, including N-7-methylguanosine (m7G), are pivotal in governing RNA stability and gene expression regulation. The accurate detection of internal m7G modifications is of paramount significance, given recent associations between altered m7G deposition and elevated expression of the methyltransferase METTL1 in various human cancers. The development of robust m7G detection techniques has posed a significant challenge in the field of epitranscriptomics. In this study, we introduce two methodologies for the global and accurate identification of m7G modifications in human RNA. We introduce borohydride reduction sequencing (Bo-Seq), which provides base resolution mapping of m7G modifications. Bo-Seq achieves exceptional performance through the optimization of RNA depurination and scission, involving the strategic use of high concentrations of NaBH4, neutral pH and the addition of 7-methylguanosine monophosphate (m7GMP) during the reducing reaction. Notably, compared to NaBH4-based methods, Bo-Seq enhances the m7G detection performance, and simplifies the detection process, eliminating the necessity for intricate chemical steps and reducing the protocol duration. In addition, we present an antibody-based approach, which enables the assessment of m7G relative levels across RNA molecules and biological samples, however it should be used with caution due to limitations associated with variations in antibody quality between batches. In summary, our novel approaches address the pressing need for reliable and accessible methods to detect RNA m7G methylation in human cells. These advancements hold the potential to catalyse future investigations in the critical field of epitranscriptomics, shedding light on the complex regulatory roles of m7G in gene expression and its implications in cancer biology.

Published
2024

18. Beyond Basic Characterization and Omics: Immunomodulatory Roles of Platelet-Derived Extracellular Vesicles Unveiled by Functional Testing

Author

Palviainen, Mari, primary, Puutio, Johanna, additional, Østergaard, Rikke Halse, additional, Eble, Johannes A, additional, Maaninka, Katariina, additional, Ndika, Joseph, additional, Kari, Otto K, additional, Kamali-Moghaddam, Masood, additional, Kjær-Sørensen, Kasper, additional, Oxvig, Claus, additional, Aransay, Ana M, additional, Falcon-Perez, Juan M, additional, Federico, Antonio, additional, Greco, Dario, additional, Laitinen, Saara, additional, Hayashi, Yuya, additional, and Siljander, Pia R-M, additional

Published
2024
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19. Inhibition of BRD4 Attenuates ER Stress-induced Renal Ischemic-Reperfusion Injury

Author

Diaz-Bulnes, Paula, primary, Rodríguez, Ramon M, additional, Banon-Maneus, Elisenda, additional, Saiz, María Laura, additional, Bernet, Cristian Ruiz, additional, Corte-Iglesias, Viviana, additional, Ramirez-Bajo, Maria Jose, additional, Lazo-Rodriguez, Marta, additional, Tamargo-Gómez, Isaac, additional, Rodrigues-Diez, Raúl R., additional, Sanz, Ana B, additional, Diaz-Corte, Carmen, additional, Ruiz-Ortega, Marta, additional, Diekmann, Fritz, additional, Aransay, Ana M, additional, Lopez-Larrea, Carlos, additional, and Suarez-Alvarez, Beatriz, additional

Published
2024
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20. A synthetic CRISPR-Cas nuclease with expanded enzymatic activities

Author

Jabalera, Ylenia, primary, Tascon, Igor, additional, Samperio, Sara, additional, Lopez-Alonso, Jorge P., additional, Gonzalez-Lopez, Monika, additional, Aransay, Ana M, additional, Abascal-Palacios, Guillermo, additional, Ubarretxena-Belandia, Iban, additional, and Perez-Jimenez, Raul, additional

Published
2023
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22. Impaired function of solute carrier family 19 leads to low folate levels and lipid droplet accumulation in hepatocytes

Author

Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo, Fundación la Caixa, European Commission, Ministerio de Economía y Competitividad (España), Institut National de la Santé et de la Recherche Médicale (France), Instituto de Salud Carlos III, Eusko Jaurlaritza, Fundación BBVA, Cano, Ainara [0000-0001-6019-8926], Vazquez-Chantada, Mercedes [0000-0002-5665-2548], Conde-Vancells, Javier [0000-0003-2791-2678], Mosen-Ansorena, David [0000-0003-4874-7931], Blanco, Francisco J. [0000-0003-2545-4319], Cleḿent, Karine [0000-0002-2489-3355], Aron-Wisnewsky, Judith [0000-0002-3104-9769], Gual, Philippe [0000-0001-7393-8356], García-Monzón, Carmelo [0000-0002-2118-8706], Martínez-Chantar, María Luz [0000-0002-6446-9911], Mato, José M. [0000-0003-1264-3153], Aransay, Ana M. [0000-0002-0013-3052], Cano, Ainara, Vazquez-Chantada, Mercedes, Conde-Vancells, Javier, Gonzalez-Lahera, Aintzane, Mosen-Ansorena, David, Blanco, Francisco J., Cleḿent, Karine, Aron-Wisnewsky, Judith, Tran, Albert, Gual, Philippe, García-Monzón, Carmelo, Caballería, Joan, Castro, Azucena, Martínez-Chantar, María Luz, Mato, José M., Zhu, Huiping, Finnell, Richard H., Aransay, Ana M., Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo, Fundación la Caixa, European Commission, Ministerio de Economía y Competitividad (España), Institut National de la Santé et de la Recherche Médicale (France), Instituto de Salud Carlos III, Eusko Jaurlaritza, Fundación BBVA, Cano, Ainara [0000-0001-6019-8926], Vazquez-Chantada, Mercedes [0000-0002-5665-2548], Conde-Vancells, Javier [0000-0003-2791-2678], Mosen-Ansorena, David [0000-0003-4874-7931], Blanco, Francisco J. [0000-0003-2545-4319], Cleḿent, Karine [0000-0002-2489-3355], Aron-Wisnewsky, Judith [0000-0002-3104-9769], Gual, Philippe [0000-0001-7393-8356], García-Monzón, Carmelo [0000-0002-2118-8706], Martínez-Chantar, María Luz [0000-0002-6446-9911], Mato, José M. [0000-0003-1264-3153], Aransay, Ana M. [0000-0002-0013-3052], Cano, Ainara, Vazquez-Chantada, Mercedes, Conde-Vancells, Javier, Gonzalez-Lahera, Aintzane, Mosen-Ansorena, David, Blanco, Francisco J., Cleḿent, Karine, Aron-Wisnewsky, Judith, Tran, Albert, Gual, Philippe, García-Monzón, Carmelo, Caballería, Joan, Castro, Azucena, Martínez-Chantar, María Luz, Mato, José M., Zhu, Huiping, Finnell, Richard H., and Aransay, Ana M.

Abstract

Low serum folate levels are inversely related to metabolic associated fatty liver disease (MAFLD). The role of the folate transporter gene (SLC19A1) was assessed to clarify its involvement in lipid accumulation during the onset of MAFLD in humans and in liver cells by genomic, transcriptomic, and metabolomic techniques. Genotypes of 3 SNPs in a case-control cohort were initially correlated to clinical and serum MAFLD markers. Subsequently, the expression of 84 key genes in response to the loss of SLC19A1 was evaluated with the aid of an RT2 profiler-array. After shRNA-silencing of SLC19A1 in THLE2 cells, folate and lipid levels were measured by ELISA and staining techniques, respectively. In addition, up to 482 amino acids and lipid metabolites were semi-quantified in SLC19A1-knockdown (KD) cells through ultra-high-performance liquid chromatography coupled with mass spectrometry. SNPs, rs1051266 and rs3788200, were significantly associated with the development of fatty liver for the single-marker allelic test. The minor alleles of these SNPs were associated with a 0.6/−1.67-fold decreased risk of developing MAFLD. When SLC19A1 was KD in THLE2 cells, intracellular folate content was four times lower than in wild-type cells. The lack of functional SLC19A1 provoked significant changes in the regulation of genes associated with lipid droplet accumulation within the cell and the onset of NAFLD. Metabolomic analyses showed a highly altered profile, where most of the species that accumulated in SLC19A1-KD-cells belong to the chemical groups of triacylglycerols, diacylglycerols, polyunsaturated fatty acids, and long chain, highly unsaturated cholesterol esters. In conclusion, the lack of SLC19A1 gene expression in hepatocytes affects the regulation of key genes for normal liver function, reduces intracellular folate levels, and impairs lipid metabolism, which entails lipid droplet accumulation in hepatocytes.

Published
2023

23. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Author

Janin, Maxime, Ortiz-Barahona, Vanessa, de Moura, Manuel Castro, Martínez-Cardús, Anna, Llinàs-Arias, Pere, Soler, Marta, Nachmani, Daphna, Pelletier, Joffrey, Schumann, Ulrike, Calleja-Cervantes, Maria E., Moran, Sebastian, Guil, Sonia, Bueno-Costa, Alberto, Piñeyro, David, Perez-Salvia, Montserrat, Rosselló-Tortella, Margalida, Piqué, Laia, Bech-Serra, Joan J., De La Torre, Carolina, Vidal, August, Martínez-Iniesta, María, Martín-Tejera, Juan F., Villanueva, Alberto, Arias, Alexandra, Cuartas, Isabel, Aransay, Ana M., La Madrid, Andres Morales, Carcaboso, Angel M., Santa-Maria, Vicente, Mora, Jaume, Fernandez, Agustin F., Fraga, Mario F., Aldecoa, Iban, Pedrosa, Leire, Graus, Francesc, Vidal, Noemi, Martínez-Soler, Fina, Tortosa, Avelina, Carrato, Cristina, Balañá, Carme, Boudreau, Matthew W., Hergenrother, Paul J., Kötter, Peter, Entian, Karl-Dieter, Hench, Jürgen, Frank, Stephan, Mansouri, Sheila, Zadeh, Gelareh, Dans, Pablo D., Orozco, Modesto, Thomas, George, Blanco, Sandra, Seoane, Joan, Preiss, Thomas, Pandolfi, Pier Paolo, and Esteller, Manel

Published
2019
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24. Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia

Author

Clos-Garcia, Marc, Andrés-Marin, Naiara, Fernández-Eulate, Gorka, Abecia, Leticia, Lavín, José L., van Liempd, Sebastiaan, Cabrera, Diana, Royo, Félix, Valero, Alejandro, Errazquin, Nerea, Vega, María Cristina Gómez, Govillard, Leila, Tackett, Michael R., Tejada, Genesis, Gónzalez, Esperanza, Anguita, Juan, Bujanda, Luis, Orcasitas, Ana María Callejo, Aransay, Ana M., Maíz, Olga, López de Munain, Adolfo, and Falcón-Pérez, Juan Manuel

Published
2019
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26. Factor-inhibiting HIF (FIH) promotes lung cancer progression

Author

García-del Río, Ana, primary, Prieto-Fernández, Endika, additional, Egia-Mendikute, Leire, additional, Antoñana-Vildosola, Asier, additional, Jimenez-Lasheras, Borja, additional, Lee, So Young, additional, Barreira-Manrique, Adrián, additional, Zanetti, Samanta Romina, additional, de Blas, Ander, additional, Velasco-Beltrán, Paloma, additional, Bosch, Alexandre, additional, Aransay, Ana M., additional, and Palazon, Asis, additional

Published
2023
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27. BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates

Author

Rueda-Alana, Eneritz, primary, Grillo, Marco, additional, Vazquez, Enrique, additional, Marco Salas, Sergio, additional, Senovilla-Ganzo, Rodrigo, additional, Escobar, Laura, additional, Quintas, Ana, additional, Benguria, Alberto, additional, Aransay, Ana M, additional, Dopazo, Ana, additional, Encinas, Juan M, additional, Nilsson, Mats, additional, and Garcia-Moreno, Fernando, additional

Published
2023
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30. SERS analysis of cancer cell-secreted purines reveals a unique paracrine crosstalk in MTAP-deficient tumors.

Author

Valera, Pablo S., Plou, Javier, García, Isabel, Astobiza, Ianire, Viera, Cristina, Aransay, Ana M., Martin, José E., Sasselli, Ivan R., Carracedo, Arkaitz, and Liz-Marzán, Luis M.

Subjects
SERS spectroscopy, PURINES, STROMAL cells, CANCER cells, TUMOR microenvironment, REMANUFACTURING
Abstract

The tumor microenvironment (TME) is a dynamic pseudoorgan that shapes the development and progression of cancers. It is a complex ecosystem shaped by interactions between tumor and stromal cells. Although the traditional focus has been on the paracrine communication mediated by protein messengers, recent attention has turned to the metabolic secretome in tumors. Metabolic enzymes, together with exchanged substrates and products, have emerged as potential biomarkers and therapeutic targets. However, traditional techniques for profiling secreted metabolites in complex cellular contexts are limited. Surface-enhanced Raman scattering (SERS) has emerged as a promising alternative due to its nontargeted nature and simplicity of operation. Although SERS has demonstrated its potential for detecting metabolites in biological settings, its application in deciphering metabolic interactions within multicellular systems like the TME remains underexplored. In this study, we introduce a SERS-based strategy to investigate the secreted purine metabolites of tumor cells lacking methylthioadenosine phosphorylase (MTAP), a common genetic event associated with poor prognosis in various cancers. Our SERS analysis reveals that MTAP-deficient cancer cells selectively produce methylthioadenosine (MTA), which is taken up and metabolized by fibroblasts. Fibroblasts exposed to MTA exhibit: i) molecular reprogramming compatible with cancer aggressiveness, ii) a significant production of purine derivatives that could be readily recycled by cancer cells, and iii) the capacity to secrete purine derivatives that induce macrophage polarization. Our study supports the potential of SERS for cancer metabolism research and reveals an unprecedented paracrine crosstalk that explains TME reprogramming in MTAP-deleted cancers. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn's Disease Patients and Effect of Anti-TNF-α Treatment on Their Modulation.

Author

Baldan-Martin, Montse, Rubín de Célix, Cristina, Orejudo, Macarena, Ortega Moreno, Lorena, Fernández-Tomé, Samuel, Soleto, Irene, Ramirez, Cristina, Arroyo, Ricardo, Fernández, Paloma, Santander, Cecilio, Moreno-Monteagudo, José Andrés, Casanova, María José, Casals, Fernando, Casabona, Sergio, Becerro, Irene, Lozano, Juan J., Aransay, Ana M., Chaparro, María, and Gisbert, Javier P.

Subjects
CROHN'S disease, LINCRNA, ILEUM, GENE expression, COLON (Anatomy), INTESTINAL mucosa
Abstract

Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Suppl Table 2 from CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

Author

Cortazar, Ana R., primary, Torrano, Veronica, primary, Martín-Martín, Natalia, primary, Caro-Maldonado, Alfredo, primary, Camacho, Laura, primary, Hermanova, Ivana, primary, Guruceaga, Elizabeth, primary, Lorenzo-Martín, Luis F., primary, Caloto, Ruben, primary, Gomis, Roger R., primary, Apaolaza, Iñigo, primary, Quesada, Victor, primary, Trka, Jan, primary, Gomez-Muñoz, Antonio, primary, Vincent, Silvestre, primary, Bustelo, Xose R., primary, Planes, Francisco J., primary, Aransay, Ana M., primary, and Carracedo, Arkaitz, primary

Published
2023
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33. Data from CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

Author

Cortazar, Ana R., primary, Torrano, Veronica, primary, Martín-Martín, Natalia, primary, Caro-Maldonado, Alfredo, primary, Camacho, Laura, primary, Hermanova, Ivana, primary, Guruceaga, Elizabeth, primary, Lorenzo-Martín, Luis F., primary, Caloto, Ruben, primary, Gomis, Roger R., primary, Apaolaza, Iñigo, primary, Quesada, Victor, primary, Trka, Jan, primary, Gomez-Muñoz, Antonio, primary, Vincent, Silvestre, primary, Bustelo, Xose R., primary, Planes, Francisco J., primary, Aransay, Ana M., primary, and Carracedo, Arkaitz, primary

Published
2023
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34. Supplementary Figure legends from CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

Author

Cortazar, Ana R., primary, Torrano, Veronica, primary, Martín-Martín, Natalia, primary, Caro-Maldonado, Alfredo, primary, Camacho, Laura, primary, Hermanova, Ivana, primary, Guruceaga, Elizabeth, primary, Lorenzo-Martín, Luis F., primary, Caloto, Ruben, primary, Gomis, Roger R., primary, Apaolaza, Iñigo, primary, Quesada, Victor, primary, Trka, Jan, primary, Gomez-Muñoz, Antonio, primary, Vincent, Silvestre, primary, Bustelo, Xose R., primary, Planes, Francisco J., primary, Aransay, Ana M., primary, and Carracedo, Arkaitz, primary

Published
2023
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35. Suppl Table 1 from CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

Author

Cortazar, Ana R., primary, Torrano, Veronica, primary, Martín-Martín, Natalia, primary, Caro-Maldonado, Alfredo, primary, Camacho, Laura, primary, Hermanova, Ivana, primary, Guruceaga, Elizabeth, primary, Lorenzo-Martín, Luis F., primary, Caloto, Ruben, primary, Gomis, Roger R., primary, Apaolaza, Iñigo, primary, Quesada, Victor, primary, Trka, Jan, primary, Gomez-Muñoz, Antonio, primary, Vincent, Silvestre, primary, Bustelo, Xose R., primary, Planes, Francisco J., primary, Aransay, Ana M., primary, and Carracedo, Arkaitz, primary

Published
2023
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36. Data from PPARδ Elicits Ligand-Independent Repression of Trefoil Factor Family to Limit Prostate Cancer Growth

Author

Martín-Martín, Natalia, primary, Zabala-Letona, Amaia, primary, Fernández-Ruiz, Sonia, primary, Arreal, Leire, primary, Camacho, Laura, primary, Castillo-Martin, Mireia, primary, Cortazar, Ana R., primary, Torrano, Verónica, primary, Astobiza, Ianire, primary, Zúñiga-García, Patricia, primary, Ugalde-Olano, Aitziber, primary, Loizaga-Iriarte, Ana, primary, Unda, Miguel, primary, Valcárcel-Jiménez, Lorea, primary, Arruabarrena-Aristorena, Amaia, primary, Piva, Marco, primary, Sánchez-Mosquera, Pilar, primary, Aransay, Ana M., primary, Gomez-Muñoz, Antonio, primary, Barrio, Rosa, primary, Sutherland, James D., primary, and Carracedo, Arkaitz, primary

Published
2023
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37. Suppl Figures 1, 2, 3, 4, 5, 6 and legends from PPARδ Elicits Ligand-Independent Repression of Trefoil Factor Family to Limit Prostate Cancer Growth

Author

Martín-Martín, Natalia, primary, Zabala-Letona, Amaia, primary, Fernández-Ruiz, Sonia, primary, Arreal, Leire, primary, Camacho, Laura, primary, Castillo-Martin, Mireia, primary, Cortazar, Ana R., primary, Torrano, Verónica, primary, Astobiza, Ianire, primary, Zúñiga-García, Patricia, primary, Ugalde-Olano, Aitziber, primary, Loizaga-Iriarte, Ana, primary, Unda, Miguel, primary, Valcárcel-Jiménez, Lorea, primary, Arruabarrena-Aristorena, Amaia, primary, Piva, Marco, primary, Sánchez-Mosquera, Pilar, primary, Aransay, Ana M., primary, Gomez-Muñoz, Antonio, primary, Barrio, Rosa, primary, Sutherland, James D., primary, and Carracedo, Arkaitz, primary

Published
2023
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38. Supplementary figures from CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets

Author

Cortazar, Ana R., primary, Torrano, Veronica, primary, Martín-Martín, Natalia, primary, Caro-Maldonado, Alfredo, primary, Camacho, Laura, primary, Hermanova, Ivana, primary, Guruceaga, Elizabeth, primary, Lorenzo-Martín, Luis F., primary, Caloto, Ruben, primary, Gomis, Roger R., primary, Apaolaza, Iñigo, primary, Quesada, Victor, primary, Trka, Jan, primary, Gomez-Muñoz, Antonio, primary, Vincent, Silvestre, primary, Bustelo, Xose R., primary, Planes, Francisco J., primary, Aransay, Ana M., primary, and Carracedo, Arkaitz, primary

Published
2023
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39. Suppl Table S1 from PPARδ Elicits Ligand-Independent Repression of Trefoil Factor Family to Limit Prostate Cancer Growth

Author

Martín-Martín, Natalia, primary, Zabala-Letona, Amaia, primary, Fernández-Ruiz, Sonia, primary, Arreal, Leire, primary, Camacho, Laura, primary, Castillo-Martin, Mireia, primary, Cortazar, Ana R., primary, Torrano, Verónica, primary, Astobiza, Ianire, primary, Zúñiga-García, Patricia, primary, Ugalde-Olano, Aitziber, primary, Loizaga-Iriarte, Ana, primary, Unda, Miguel, primary, Valcárcel-Jiménez, Lorea, primary, Arruabarrena-Aristorena, Amaia, primary, Piva, Marco, primary, Sánchez-Mosquera, Pilar, primary, Aransay, Ana M., primary, Gomez-Muñoz, Antonio, primary, Barrio, Rosa, primary, Sutherland, James D., primary, and Carracedo, Arkaitz, primary

Published
2023
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40. 62 - EFECTO EX VIVO DE INFLIXIMAB EN LOS NIVELES DE EXPRESIÓN DE LOS LONG NON-CODING RNAS EN LA ENFERMEDAD DE CROHN

Author

Baldán-Martín, Montse, primary, de Célix, Cristina Rubín, additional, Orejudo, Macarena, additional, Ortega, Lorena, additional, Tomé, Samuel Fernández, additional, Soleto, Irene, additional, Ramirez, Cristina, additional, Arroyo, Ricardo, additional, Fernández, Paloma, additional, Santander, Cecilio, additional, Moreno-Monteagudo, José Andrés, additional, Casanova, María José, additional, Casals, Fernando, additional, Casabona, Sergio, additional, Becerro, Irene, additional, Marigorta, Urko M., additional, Aransay, Ana M., additional, Bernardo, David, additional, Chaparro, María, additional, and Gisbert, Javier P., additional

Published
2023
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41. Introduction

Author

Rodríguez-Ezpeleta, Naiara, Aransay, Ana M., Rodríguez-Ezpeleta, Naiara, editor, Hackenberg, Michael, editor, and Aransay, Ana M., editor

Published
2012
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42. METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Author

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, 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, and Blanco, Sandra

Abstract

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.

Published
2023

43. N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer

Author

Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Castilla y León, Banco Santander, Universidad de Salamanca, Asociación Española Contra el Cáncer, European Commission, Consejo Superior de Investigaciones Científicas (España), Añazco-Guenkova, Ana M. [0000-0001-6483-0415], García-Vílchez, Raquel, Añazco-Guenkova, Ana M., López, Judith, Dietmann, Sabine, Tomé, Mercedes, Jimeno, Sonia, Azkargorta, Mikel, Elortza, Félix, Bárcena, Laura, Gonzalez-Lopez, Monika, Aransay, Ana M., Sánchez-Martín, Manuel A., Huertas, Pablo, Durán, Raúl V., Blanco, Sandra, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Castilla y León, Banco Santander, Universidad de Salamanca, Asociación Española Contra el Cáncer, European Commission, Consejo Superior de Investigaciones Científicas (España), Añazco-Guenkova, Ana M. [0000-0001-6483-0415], García-Vílchez, Raquel, Añazco-Guenkova, Ana M., López, Judith, Dietmann, Sabine, Tomé, Mercedes, Jimeno, Sonia, Azkargorta, Mikel, Elortza, Félix, Bárcena, Laura, Gonzalez-Lopez, Monika, Aransay, Ana M., Sánchez-Martín, Manuel A., Huertas, Pablo, Durán, Raúl V., and Blanco, Sandra

Abstract

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that N7-guanosine methylation (m7G) of tRNAs, mediated by METTL1, regulates survival to stress conditions in cancer cells. Mechanistically, we find that m7G in tRNAs protects them from stress-induced cleavage and processing into 5' tRNA fragments. Our analyses reveal that the loss of tRNA m7G methylation activates stress response pathways, sensitising cancer cells to stress. Furthermore, we find that the loss of METTL1 reduces tumour growth and increases cytotoxic stress in vivo. Our study uncovers the role of m7G methylation of tRNAs in stress responses and highlights the potential of targeting METTL1 to sensitise cancer cells to chemotherapy.

Published
2023

44. Additional file 10 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

45. Additional file 7 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

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, 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, and Blanco, Sandra

Published
2023

46. Additional file 8 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

47. Additional file 9 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

48. Additional file 2 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

49. Additional file 3 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

50. Additional file 4 of METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [Dataset]

Author

Consejo Superior de Investigaciones Científicas (España), 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, Consejo Superior de Investigaciones Científicas (España), 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, and Blanco, Sandra

Published
2023

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