Dissecting the role of KRAS-driven miRNAs in Lung Cancer
Lung cancer is the deadliest cancer in U.S. Lung cancer involves two major groups, Small-Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC). NSCLC represents 80% of lung cancer cases, and includes the most prevalent lung cancer subtype, lung adenocarcinoma (LUAD). Around 30% of LUAD patients harbor mutations in KRAS oncogene. However, mutant KRAS remains refractile to pharmacological inhibition. Thus, a more detailed insight on the functional and molecular mechanisms involved in oncogenic KRAS signaling as well as their clinical impact in LUAD remains imperative for the identification of novel target genes.
MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional regulators of mRNA target genes, and have been involved in a plethora of biological functions. Preliminary results from our group unveiled a miRNA cluster as a potential downstream effector of oncogenic KRAS. Of note, genetic germ-line and conditional deletion of the cluster containing this cluster using genetically-engineered mouse models led to decreased tumor burden and increased overall survival, what strongly suggest a prominent role in LUAD. Thus, the current proposal will follow an integrative approach using mouse genetics, in vitro analysis and human specimens to delineate the functional and clinical role of this miRNA cluster in KRAS-driven LUAD.
- Duration: 3 años
- Start date: January 1, 2016
- End date: December 31, 2019
- Funder: Worldwide Cancer Research (16-0224)
- Grant: 159.000 €
- Nature of project: International