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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. RNA Networks and Biology
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1471100

Long non-coding RNA GRASLND links melanoma differentiation and interferon-gamma response

Provisionally accepted
Kim D. Fischer Kim D. Fischer 1,2Shashank Tiwari Shashank Tiwari 1,2Beatrice Thier Beatrice Thier 3Lin C. Qiu Lin C. Qiu 1,2Tzu-Chen Lin Tzu-Chen Lin 4,5Annette Paschen Annette Paschen 3Jochen Imig Jochen Imig 1,2*
  • 1 Max Planck Institute for Molecular Physiology, Dortmund, Germany
  • 2 Chemical Genomics Centre Of the Max Planck Society, Dortmund, Germany
  • 3 University Hospital Essen, Department of Dermatology, Essen, Germany
  • 4 Technical University Dortmund, Dortmund, North Rhine-Westphalia, Germany
  • 5 Faculty of Chemistry and Chemical Biology, Dortmund, Germany

The final, formatted version of the article will be published soon.

    Melanoma is a highly malignant tumor, that stands as the most lethal form of skin cancer and is characterized by notable phenotypic plasticity and intratumoral heterogeneity. Melanoma plasticity is involved in tumor growth, metastasis and therapy resistance. Long non-coding RNAs (lncRNAs) could influence plasticity due to their regulatory function. However, their role and mode of action are poorly studied. Here, we show a relevance of lncRNA GRASLND in melanoma differentiation and IFNγ signaling. GRASLND knockdown revealed switching of differentiated, melanocytic melanoma cells towards a dedifferentiated, slow-proliferating and highly-invasive cell state. Interestingly, GRASLND is overexpressed in differentiated melanomas and associated with poor prognosis. Accordingly, we found GRASLND expressed in immunological “cold” tumors and it negatively correlates with gene signatures of immune response activation. In line, silencing of GRASLND under IFNγ enhanced the expression of IFNγ-stimulated genes, including HLA-I antigen presentation, demonstrating suppressive activity of GRASLND on IFNγ signaling. Our findings demonstrate that in differentiated melanomas elevated expression of GRASLND interferes with anti-tumor effects of IFNγ, suggesting a role of GRASLND in tumor immune evasion.

    Keywords: Melanoma, lncRNA, Phenotypic switch, differentiation, IFNγ response

    Received: 26 Jul 2024; Accepted: 13 Sep 2024.

    Copyright: © 2024 Fischer, Tiwari, Thier, Qiu, Lin, Paschen and Imig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jochen Imig, Max Planck Institute for Molecular Physiology, Dortmund, Germany

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