STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis

Abstract

The role of signal transducer and activator of transcription 6 (STAT6) in tumor growth has been widely recognized. However, its effects on the regulation of angiogenesis remain unclear. In this study, we found that STAT6 promoted angiogenesis, possibly by increasing the expression of neuropilin-1 (NRP1) in endothelial cells (ECs). Both STAT6 inhibitor (AS1517499) and STAT6 siRNA reduced EC proliferation, migration, and tube-formation, accompanied by downregulation of NRP1, an angiogenesis regulator. Furthermore, IL-13 induced activation of STAT6 and then increased NRP1 expression in ECs. IL-13-induced EC migration and tube formation were inhibited by NRP1 siRNA. Luciferase assay and chromatin immunoprecipitation assay demonstrated that STAT6 could directly bind to human NRP1 promoter and increase the promoter activity. In tumor xenograft models, inhibition of STAT6 reduced xenograft growth, tumor angiogenesis, and NRP1 expression in vivo. Overall, these results clarified the novel mechanism by which STAT6 regulates angiogenesis, and suggested that STAT6 may be a potential target for anti-angiogenesis therapy.

m6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression

“…Here, we pointed out that IGF2BP2, as an m6A reader, recognized and bound to the m6A modified region of NRP1 transcript to enhance NRP1 mRNA stability. NRP1 is commonly expressed in endothelial cells and some tumor cells, and plays an important function in angiogenesis and tumorigenesis [ 38 , 39 ]. In many cancers, NRP1 serves as tumor promoter to participate in development of many cancers, including gastric cancer [ 40 ] and lung cancer [ 41 ].…”