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

Abstract

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 (), as essential for the lymphedema development.is the most expressed lncRNA in human lymphatic endothelial cells (LECs) under stress condition. Knocking downin LECs promotes the expression of inflammation-related genes. Mechanistically, ATAC-seq revealed thatinduces the transcription of genes involved in lymphangiogenesis and immune cell adhesion by increasing chromatin accessibility. Notably,deficiency impairs LEC proliferation, migration, and sprouting. Conditional deletion ofin mouse lymphatic endothelium (Lnc-Pint) leads to a reduction in dermal lymphatic network density. Lnc-Pintmice exhibit decreased lymphedema, reduced dermal backflow, fibrosis, and inflammation. Our findings unveil a crucial molecular role ofin lymphatic function and hold substantial clinical implications for lncRNA as biomarker of lymphedema.