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长链非编码RNA GRASLND与黑色素瘤分化和γ-干扰素反应相关。

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

作者信息

Fischer Kim Denise, Tiwari Shashank, Thier Beatrice, Qiu Lin Christina, Lin Tzu-Chen, Paschen Annette, Imig Jochen

机构信息

Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Faculty of Chemistry and Chemical Biology, Technical University of Dortmund, Dortmund, Germany.

出版信息

Front Mol Biosci. 2024 Sep 27;11:1471100. doi: 10.3389/fmolb.2024.1471100. eCollection 2024.

DOI:10.3389/fmolb.2024.1471100
PMID:39398277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11466874/
Abstract

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.

摘要

黑色素瘤是一种高度恶性的肿瘤，是皮肤癌中最致命的形式，具有显著的表型可塑性和肿瘤内异质性。黑色素瘤的可塑性与肿瘤生长、转移和治疗抗性有关。长链非编码RNA（lncRNAs）因其调控功能可能影响可塑性。然而，它们的作用和作用方式研究较少。在这里，我们展示了lncRNA GRASLND在黑色素瘤分化和IFNγ信号传导中的相关性。GRASLND敲低揭示了分化的黑素细胞性黑色素瘤细胞向去分化、增殖缓慢和高侵袭性细胞状态的转变。有趣的是，GRASLND在分化的黑色素瘤中过表达，且与预后不良相关。因此，我们发现GRASLND在免疫“冷”肿瘤中表达，并且它与免疫反应激活的基因特征呈负相关。同样，在IFNγ作用下沉默GRASLND可增强IFNγ刺激基因的表达，包括HLA-I抗原呈递，证明GRASLND对IFNγ信号传导具有抑制活性。我们的研究结果表明，在分化的黑色素瘤中，GRASLND的高表达会干扰IFNγ的抗肿瘤作用，提示GRASLND在肿瘤免疫逃逸中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/60b79d1bb047/fmolb-11-1471100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/6876fc46f0fd/fmolb-11-1471100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/89b715fd0c1f/fmolb-11-1471100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/8fada12b68a3/fmolb-11-1471100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/65cb448ac379/fmolb-11-1471100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/4cbe5f29d36d/fmolb-11-1471100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/60b79d1bb047/fmolb-11-1471100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/6876fc46f0fd/fmolb-11-1471100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/89b715fd0c1f/fmolb-11-1471100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/8fada12b68a3/fmolb-11-1471100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/65cb448ac379/fmolb-11-1471100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/4cbe5f29d36d/fmolb-11-1471100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f23/11466874/60b79d1bb047/fmolb-11-1471100-g006.jpg

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Mol Cell Biochem. 2025 Feb;480(2):1155-1167. doi: 10.1007/s11010-024-05045-6. Epub 2024 Jun 15.
3
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Heliyon. 2024 Apr 1;10(7):e29071. doi: 10.1016/j.heliyon.2024.e29071. eCollection 2024 Apr 15.
4
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5
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Cell Mol Biol Lett. 2022 Jun 15;27(1):48. doi: 10.1186/s11658-022-00353-5.
6
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Cureus. 2022 May 8;14(5):e24818. doi: 10.7759/cureus.24818. eCollection 2022 May.
7
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