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Updated: Jul 24, 2025

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
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Musashi-2 (MSI2) regulation of DNA damage response in lung cancer

Igor Bychkov, Alexander Deneka, Iuliia Topchu

    Biorxiv : the Preprint Server for Biology
    |July 3, 2023
    PubMed

    Insights

    Musashi-2 (MSI2) promotes non-small cell lung cancer (NSCLC) by regulating ATM expression and DNA damage response. Targeting MSI2 may offer a new strategy for treating lung cancer.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • Non-small cell lung cancer (NSCLC) is a major global health concern, often driven by KRAS and TP53 mutations.
    • Overexpression of the RNA-binding protein Musashi-2 (MSI2) is linked to NSCLC progression.
    • The precise role of MSI2 in NSCLC tumorigenesis requires further elucidation.

    Approach:

    • Compared lung tumorigenesis in mice with Kras-activating mutations and Trp53 deletion, with and without Msi2 deletion (KP vs. KPM2).
    • Investigated MSI2's direct interaction with ATM/Atm mRNA and its translational regulation using NSCLC cell lines.
    • Assessed the impact of MSI2 depletion on DNA damage response (DDR) signaling and sensitivity to PARP inhibitors in vitro and in vivo.

    Key Points:

    • Mice lacking Msi2 (KPM2) exhibited reduced lung tumorigenesis compared to control mice (KP).
    • MSI2 directly binds and regulates ATM/Atm mRNA translation.
    • MSI2 depletion impaired DDR signaling and increased sensitivity to PARP inhibitors in NSCLC cells.

    Conclusions:

    • MSI2 supports lung tumorigenesis, partly through positive regulation of ATM protein expression and DNA damage response.
    • This study reveals a novel role for MSI2 as a regulator of ATM expression and DDR in lung cancer.
    • Targeting MSI2 presents a potential therapeutic strategy for NSCLC treatment.

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