microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.

Zhou Y, Frings O, Branca RM, Boekel J, le Sage C, Fredlund E, Agami R, Orre LM

Oncogene 36 (6) 731-745 [2017-02-09; online 2016-08-01]

microRNA (miRNA) dysregulation is a common feature of cancer cells, but the complex roles of miRNAs in cancer are not fully elucidated. Here, we used functional genomics to identify oncogenic miRNAs in non-small cell lung cancer and evaluate their impact on response to epidermal growth factor (EGFR)-targeting therapy. Our data demonstrate that miRNAs with an AAGUGC motif in their seed sequence increase both cancer cell proliferation and sensitivity to EGFR inhibitors. Global transcriptomics, proteomics and target prediction resulted in the identification of several tumor suppressors involved in the G1/S transition as AAGUGC-miRNA targets. The clinical implications of our findings were evaluated by analysis of AAGUGC-miRNA expression in multiple cancer types, supporting the link between this miRNA seed family, their tumor suppressor targets and cancer cell proliferation. In conclusion, we propose the AAGUGC seed motif as an oncomotif and that oncomotif-miRNAs promote cancer cell proliferation. These findings have potential therapeutic implications, especially in selecting patients for EGFR-targeting therapy.

Bioinformatics Support and Infrastructure [Collaborative]

Bioinformatics Support, Infrastructure and Training [Collaborative]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 27477696

DOI 10.1038/onc.2016.242

Crossref 10.1038/onc.2016.242

pii: onc2016242
pmc: PMC5311252