Article Dans Une Revue Science Advances Année : 2025

lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema

Résumé

Lymphedema is a lymphatic dysfunction leading to an accumulation of fluid and fat in the arm or leg. Here, we performed noncoding RNA profiling of human breast cancer-induced secondary lymphedema. We identified the long intergenic non-protein coding RNA, P53-induced transcript (LINC-PINT), as essential for the lymphedema development. LINC-PINT is the most expressed lncRNA in human lymphatic endothelial cells (LECs) under stress condition. Knocking down LINC-PINT in LECs promotes the expression of inflammation-related genes. Mechanistically, ATAC-seq revealed that LINC-PINT induces the transcription of genes involved in lymphangiogenesis and immune cell adhesion by increasing chromatin accessibility. Notably, LINC-PINT deficiency impairs LEC proliferation, migration, and sprouting. Conditional deletion of Lnc-Pint in mouse lymphatic endothelium (Lnc-Pint lecko ) leads to a reduction in dermal lymphatic network density. Lnc-Pint lecko mice exhibit decreased lymphedema, reduced dermal backflow, fibrosis, and inflammation. Our findings unveil a crucial molecular role of LINC-PINT in lymphatic function and hold substantial clinical implications for lncRNA as biomarker of lymphedema.

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hal-05587421 , version 1 (10-04-2026)

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Nathalie Laugero, Claire Peghaire, Léna Verdu, Elisa Balzan, Tangra Draia-Nicolau, et al.. lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema. Science Advances , 2025, 11 (51), pp.eaea2960. ⟨10.1126/sciadv.aea2960⟩. ⟨hal-05587421⟩
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