NCOA7 inhibits renal cancer progression by inducing autophagy and lipid metabolism through V-ATPase interaction

Clear cell renal cell carcinoma is the predominant pathological subtype of renal cell carcinoma, characterized by abnormal lipid metabolism. This study aimed to investigate the role of nuclear receptor co-activator 7 (NCOA7)-mediated autophagy in lipid metabolism in renal cancer and its effects on renal cancer progression. To this end, bioinformatic analysis was performed to analyze the prognostic significance of NCOA7 in renal cancer. Immunohistochemical staining and protein blotting were used to assess NCOA7 expression levels in clinical samples. Various assays, including scratch, Transwell, colony formation, and Oil Red O staining, were used to observe the effects of NCOA7 on the biological behavior and lipid metabolism of renal cancer cells. The interaction between NCOA7 and V-ATPase was investigated using immunoprecipitation. Additionally, NCOA7 expression was modulated in renal cancer cell lines transfected with LC3 dual-fluorescent virus to study its effects on lysosomal function, autophagy, and lipid metabolism. The effects of NCOA7 expression levels on subcutaneous tumors were investigated using a nude mouse xenograft model. Bioinformatics analysis showed that NCOA7 was expressed at low levels in renal cancer tissues and independently associated with the prognosis in patients with renal cancer. In vitro experiments showed that high NCOA7 expression inhibited the proliferation, migration, and invasion of renal cancer cells. NCOA7 promoted the fusion of lysosomes with autophagosomes through its interaction with V-ATPase. High expression of NCOA7 enhanced autophagy and lipid metabolism and inhibited the growth of renal cancer cells. In vivo experiments showed that high NCOA7 expression inhibited the growth of subcutaneous tumors in nude mice. Our study demonstrates that NCOA7 promotes autophagy and reduces lipid accumulation by binding to V-ATPase and ultimately inhibits the progression of renal cancer. These findings suggest that NCOA7 might be a potential target for drug intervention in clear cell renal carcinoma. The schematic illustrates that NCOA7 upregulation interacts with V-ATPase to promote autophagosome-lysosome fusion, enhance autophagic degradation of lipid droplets, and thereby suppress proliferation, migration, and invasion of kidney cancer cells. Image created with BioRender.com, with permission.