lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema
- Nathalie Laugero
- Claire Peghaire
- Léna Verdu
- Elisa Balzan
- Tangra Draia-Nicolau
- Roxane Sylvestre
- Julie Malloizel-Delaunay
- Alessandra Bura-Rivière
- Florent Morfoisse
- Anne-Catherine Prats
- Eric Lacazette
- Barbara Garmy-Susini
2025-12-17
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.