UPF1-dependent glycolysis driven by LINC00887 facilitates macrophage M2 polarization in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC), a frequent urinary system tumor, is known for its poor patient outcomes. Here, we demonstrate that LINC00887 overexpression in ccRCC drives M2 macrophage polarization via aerobic glycolysis activation and lactate accumulation. Mechanistically, LINC00887 interacted with UPF1, leading to reduced UPF1 levels. UPF1, which is low in ccRCC, restrained cell vitality, proliferation, migration, invasion, and cell cycle progression in ccRCC cells, and stimulated apoptosis. Additionally, UPF1 was found to be negatively correlated with aerobic glycolysis in ccRCC, repressing glycolytic activity and M2 macrophage polarization while bolstering the tumor-killing potential of CD8+ T cells. By combining bioinformatics with experimental data from ccRCC single-cell RNA sequencing, we've demonstrated that reduced UPF1 expression can reprogram glycolytic metabolism, leading to an improved immunosuppressive tumor microenvironment. Overall design: Two pairs of pathologically confirmed ccRCC tumor tissues and their matched normal tissues were collected.After dissociation with tissue digestion solution and lysis with red blood cell lysis buffer, suspensions were obtained for scRNA-seq.