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

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....

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Autores: Valencia, K. (Karmele)|||/items/bf771eab-81c1-4221-80f5-87713ad5e51f, Erice, O. (Oihane)|||/items/2541f3e8-8d0c-4c86-89d1-c245e534633e, Kostyrko, K. (Kaja)|||/items/f4251a8e-d778-4423-b953-6d5e864b6752, Hausmann, S. (Simone)|||/items/f1edd7f7-f338-4ae8-882d-181c9e453728, Guruceaga-Martínez, E. (Elizabeth)|||/items/71d8df8b-4fab-4004-a38e-4057dddc85b2, Tathireddy, A. (Anuradha)|||/items/e7105a7d-989a-41c2-afb0-987a29713171, Flores, N.M. (Natasha M.)|||/items/48851fda-c7ad-499a-82e5-030e691f21dd, Sayles, L.C. (Leanne C.)|||/items/59715ff6-fd7b-4ee9-9974-e980c5bdea70, Lee, A.G. (Alex G.)|||/items/63c35de7-4b7d-441f-ae54-dada8cf8262a, Fragoso, R. (Rita)|||/items/90d0a5b6-5e3d-425b-a3b9-03c4430ecca2, Sun, T.Q. (Tian-Qiang)|||/items/52c76c65-9abb-4f59-b246-8ae9b9957dee, Vallejo, A. (Adrian)|||/items/84c6e1dc-a9d4-4c6d-95e4-a8ea6e841633, Román, M. (Marta)|||/items/1d15a7c2-01b3-4b6f-b702-1fac9a119892, Entrialgo-Cadierno, R. (Rodrigo)|||/items/0ac6fab0-1703-4571-929b-363e142032ac, Miguéliz-Basterra, I. (Itziar)|||/items/f8b05fe5-028a-4ebf-a3d8-bff420f4b61d, Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d, Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e, Lecanda, F. (Fernando)|||/items/3fac5441-504d-4927-979a-5460140b12ec, Lu, J. (Jun)|||/items/c97b6459-aceb-4dde-8e13-aa80f7d3f0cd, Ponz-Sarvise, M. (Mariano)|||/items/2439c580-068e-431b-a20d-bdeab1b7c3ad, Chen, C.Z. (Chang-Zheng)|||/items/05e87ba4-33ba-4f26-8888-88659958ca47, Mazur, P.K. (Pawel K.)|||/items/ac9e28fb-f921-49ce-b787-6cf343c678b9, Sweet-Cordero, E.A. (E. Alejandro)|||/items/59fc55cd-7e48-40a5-ad8a-9595bcf14630, Vicent-Cambra, S. (Silvestre)|||/items/20c60fd9-edba-4dba-942c-3669eb079816
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/67936
Acceso en línea:https://hdl.handle.net/10171/67936
Access Level:acceso abierto
Palabra clave:KRAS-driven cancers
New molecular targets
microRNA (miRNA)
Oncogenesis
Descripción
Sumario: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.

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