Scientific publications

The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas

Apr 1, 2020 | Magazine: Journal of Clinical Investigation

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


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.

Our authors

Dr. Karmele Valencia Leoz
Research Collaborator Solid Tumor Research Program
Dr. Oihane Erice Azparren
Elizabet Guruceaga Martínez
Bioinformatics Research Technician Bioinformatics Platform
Adrián Vallejo Blanco
Project Graduate Solid Tumor Research Program
Rodrigo Entrialgo Cadierno
Nerea Razquin Erro