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

Oncogene (2016-08-02)
Y Zhou, O Frings, R M Branca, J Boekel, C le Sage, E Fredlund, R Agami, L M Orre
RESUMEN

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.

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Penicilina- Estreptomicina, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture
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Dulbecco′s Modified Eagle′s Medium, With 4500 mg/L glucose, stable glutamine, and sodium bicarbonate, without sodium pyruvate., liquid, sterile-filtered, suitable for cell culture
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RPMI-1640 Medium, With stable glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
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Ribonucleasa A from bovine pancreas, for molecular biology, ≥70 Kunitz units/mg protein, lyophilized
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DL-Ditiotreitol, ≥99.0% (RT)
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