Specific effects of hypoxia-immune core gene ARHGAP11A on lung adenocarcinoma.

Abstract

Background: The changes in tumor microenvironment (TME) are closely related to the regulation of immunity and hypoxia. This study aimed to investigate the specific effects of ARHGAP11A on the prognosis, immunity, and hypoxia of lung adenocarcinoma (LUAD).

Methods: The core gene ARHGAP11A related to immunity and hypoxia was obtained from a variety of databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), the Search Tool for the Retrieval of Interacting Genes (STRING), HALLMARK gene set, and various analysis methods (differences and single factor Cox analysis). The relationship between the expression level of ARHGAP11A, survival prognosis, immune invasion, and hypoxia regulation was analyzed.

Results: ARHGAP11A was associated with poor patient prognosis and was strongly associated with immune and hypoxic-related signal pathways. We also found that knocking down the expression of ARHGAP11A can affect the proliferation, glycolysis, migration, invasion, and anti-apoptotic ability of tumor cells. The changes of apoptosis-related proteins (BCL2, BAX, and Caspase-3), cell cycle protein E1, D1 (cyclin D1, cyclin E1), matrix metalloproteinase 2 and 9 (MMP2, MMP9), and P-Phosphatidylinositol 3-kinase and protein kinase B (P-PI3K and P-AKT) in the knockdown group, were verified by Western blot (WB). We also found that interfering with the expression of ARHGAP11A can reduce the expression of programmed cell death ligand 1 (PDL1) in LUAD cells. Through the induction of tumor cells by cobalt chloride (CoCL2), we established a hypoxic microenvironment, and found that interfering with ARHGAP11A can significantly reduce the expression of hypoxia-inducible factor 1A (HIF1A), downstream molecular vascular endothelial growth factor A (VEGFA), and lactate dehydrogenase A (LDHA).

Conclusions: The expression of ARHGAP11A is highly correlated with immunity, hypoxia, poor prognosis, and tumor cell development. Therefore, the study of ARHGAP11A can provide more ideas on comprehensive treatment and prognosis management of LUAD.