Changes in cell morphology and function induced by NRAS Q61R mutation in lymphatic endothelial cells

Abstract

Recently, a low-level somatic mutation in NRAS gene (c.182 A > G, Q61R) was identified in the specimens of patients with kaposiform lymphangiomatosis (KLA). However, it is unknown how these low-frequency mutated cells can affect the characterization and surrounding environment of their lesions. To understand the pathogenesis and association of these gene abnormalities, we established NRASQ61R mutated lymphatic endothelial cells (LECs) transfected with lentivirus vector and undertook morphological and functional characterization, protein expression profiling, and metabolome analysis. NRASQ61R human dermal LECs showed poor tube formation and high cell proliferation and migration ability with increasing ratios of mutated cells. Analysis of signaling pathways showed inactivation of the PIK3/AKT/mTOR pathway and hyperactivation of the RAS/MAPK/ERK pathway, which was improved by MEK inhibitor treatment. This study may show the theoretical circumstances in vitro induced by NRASQ61R-mutated cells in the affected lesions of KLA patients.