Scientific publications
- [SOLID TUMOR]
- [ONCOGENES AND EFFECTOR TARGETS]
- [ADHESION AND METASTASIS]
- [GENE THERAPY FOR RARE DISEASES]
- [THERAPEUTIC NON-CODING RNA, MICROPROTEINS AND INTEGRATED STRESS IN CANCER]
- [COMPUTATIONAL BIOLOGY AND TRANSLATIONAL GENOMICS]
- [BIOINFORMATICS]
The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas
Karmele Valencia, Oihane Erice, Kaja Kostyrko, Simone Hausmann, Elizabeth Guruceaga, Anuradha Tathireddy, Natasha M Flores, Leanne C Sayles, Alex G Lee, Rita Fragoso, Tian-Qiang Sun, Adrian Vallejo, Marta Roman, Rodrigo Entrialgo-Cadierno, Itziar Migueliz, Nerea Razquin, Puri Fortes, Fernando Lecanda, Jun Lu, Mariano Ponz-Sarvise, Chang-Zheng Chen, Pawel K Mazur, E Alejandro Sweet-Cordero, Silvestre Vicent
Abstract
Few therapies are currently available for patients with KRAS-driven cancers, highlighting the need to identify new molecular targets that modulate central downstream effector pathways. Here we found that the microRNA (miRNA) cluster including miR181ab1 is a key modulator of KRAS-driven oncogenesis. Ablation of Mir181ab1 in genetically engineered mouse models of Kras-driven lung and pancreatic cancer was deleterious to tumor initiation and progression.
Expression of both resident miRNAs in the Mir181ab1 cluster, miR181a1 and miR181b1, was necessary to rescue the Mir181ab1-loss phenotype, underscoring their nonredundant role. In human cancer cells, depletion of miR181ab1 impaired proliferation and 3D growth, whereas overexpression provided a proliferative advantage. Lastly, we unveiled miR181ab1-regulated genes responsible for this phenotype. These studies identified what we believe to be a previously unknown role for miR181ab1 as a potential therapeutic target in 2 highly aggressive and difficult to treat KRAS-mutated cancers.
CITA DEL ARTÍCULO J Clin Invest. 2020 Apr 1;130(4):1879-1895. doi: 10.1172/JCI129012.
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Our authors
![Karmele Valencia Leoz. Programa Tumores Sólidos. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-verticales/tumores-solidos/karmele-valencia-leoz/jcr:content/karmele-valencia-leoz.jpg)
![Oihane Erice. Programa Tumores Sólidos. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-verticales/tumores-solidos/oihane-erice-azparren/jcr:content/oihane-erice-azparren.jpg)
![Elisabet Guruceaga. Programa Biología Computacional. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-transversales/biologia-computacional/elisabet-guruceaga-martinez/jcr:content/elisabet-guruceaga-martinez.jpg)
![Adrián Vallejo. Programa Tumores Sólidos. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-verticales/tumores-solidos/adrian-vallejo-blanco/jcr:content/adrian-vallejo-blanco.jpg)
![Rodrigo Entrialgo Cadierno. Programa Tumores Sólidos. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-verticales/tumores-solidos/img-rodrigo-entrialgo-cadierno/jcr:content/rodrigo-entrialgo-cadierno.jpg)
![Nerea Razquin. Programa Terapia Génica. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-transversales/terapia-genica/nerea-razquin-erro/jcr:content/nerea-razquin-erro.jpg)