Signal-transducing adaptor protein 1 (STAP1) in microglia promotes the malignant progression of glioma

作者：Xinyu Yang, Chunxia Ji, Ying Qi, Jianhan Huang, Lang Hu, Yuan Zhou, Liping Zou, Yi Xia, Feng Tan, Yu Yao, Di Chen · 发表于：Research Square · 年份：2023 · DOI：10.21203/rs.3.rs-2783588/v1 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer、Chemokine receptors and signaling

Abstract Background Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays a major role in the pathogenesis of glioma. Currently, microglia (CD11b + /CD45 Low ) and macrophages (CD11b + /CD45 High ) are distinguished as distinct cell types due to their different origins. Moreover, Signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies on STAP1 in GAMs have been reported. Methods The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-Sequencing, qRT-PCR, western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscope. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mice models. Glioma growth was monitored by bioluminescence imaging. Results STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting ...