microRNA dysregulation is a common feature of cancer cells, but the complex roles of microRNAs in cancer are not fully elucidated. Here we used functional genomics to identify oncogenic microRNAs in non-small cell lung cancer and to evaluate their impact on response to EGFR targeting therapy. Our data demonstrate that microRNAs 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 targets of AAGUGC-microRNAs. The clinical implications of our findings were evaluated by analysis of public domain data supporting the link between this microRNA seed-family, their tumor suppressor targets and cancer cell proliferation. In conclusion we propose that AAGUGC-microRNAs are an integral part of an oncogenic signaling network, and that these findings have potential therapeutic implications, especially in selecting patients for EGFR-targeting therapy.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Human ; U1810 ; microRNA ; miRNA ; HiRIEF ; LC-MS
Principal Investigators: (in alphabetical order) |
Janne Lehti�, Dept. Oncology Pathology, Karolinska Institutet, and Scilifelab, Stockholm, Sweden, N/A |
Submitting User: | ccms |
Zhou Y, Frings O, Branca RM, Boekel J, le Sage C, Fredlund E, Agami R, Orre LM.
microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.
Oncogene. 2017 Feb 9;36(6):731-745. Epub 2016 Aug 1.
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