NFATc2 promotes lactate and M2 macrophage polarization through USP17 in lung adenocarcinoma.

Abstract

It is well known that immune cells including macrophages within the tumor microenvironment play an essential role in tumor progression. Here, we studied how NFATc2 regulated macrophage properties in lung adenocarcinoma. Higher expression of NFATc2 was observed in the lung adenocarcinoma tissues than in the normal lung tissues. Positive relationships were found between NFATc2 and genes associated with hypoxia and glycolysis in lung adenocarcinoma from the TCGA dataset. According to single-cell sequence data, NFATc2 was closely associated with infiltrating immune cells and was related to macrophage polarization. As a transcription factor, NFATc2 binding to the USP17 promoter region, that enhanced cell migration and lactate level in lung adenocarcinoma cells, and M2 polarization in macrophages. Furthermore, the NFATc2 inhibitor suppressed lactate and M2 macrophage polarization induced by NFATc2 and USP17. In conclusion, NFATc2 promotes lactate level and M2 macrophage polarization by transcriptionally regulating USP17 in lung adenocarcinoma.