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Updated: Mar 17, 2026

MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as a Novel Detection and Quantification Method
Published on: October 7, 2025
microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network
Y Zhou1, O Frings1, R M Branca1
1Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Abstract:
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.
Insights
Specific microRNAs (miRNAs) with an AAGUGC motif promote cancer cell growth and sensitivity to EGFR-targeted therapy. This discovery offers potential for improved cancer treatment selection.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- MicroRNA (miRNA) dysregulation is prevalent in cancer.
- The precise functions of miRNAs in oncogenesis remain incompletely understood.
- Identifying specific miRNAs driving cancer progression is crucial.
Purpose of the Study:
- To identify oncogenic miRNAs in non-small cell lung cancer (NSCLC).
- To assess the impact of identified miRNAs on response to epidermal growth factor receptor (EGFR)-targeting therapy.
- To investigate the therapeutic potential of miRNA-based biomarkers.
Main Methods:
- Functional genomics screens were employed to identify key miRNAs.
- Global transcriptomics and proteomics analyses were performed.
- Bioinformatic target prediction and clinical data analysis were utilized.
Main Results:
- MiRNAs possessing an AAGUGC seed motif were found to enhance cancer cell proliferation.
- These AAGUGC-motif miRNAs also increased sensitivity to EGFR inhibitors.
- Identified targets included tumor suppressors regulating the G1/S cell cycle transition.
Conclusions:
- The AAGUGC seed motif is proposed as an 'oncomotif' driving cancer proliferation.
- Oncomotif-miRNAs contribute to cancer cell growth and may influence therapeutic response.
- Findings suggest potential for patient stratification in EGFR-targeted therapies.
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