HOXA3 activates USP15 to suppress autophagy and promote M2-type macrophage polarization in renal cell carcinoma via facilitating the deubiquitination of SQSTM1

The disease burden of renal cell carcinoma (RCC) has decreased in recent years with advances in treatment, but its pathogeny still remains elusive. We aim to study the role of HOXA3/USP15/SQSTM1 axis on autophagy and M2-type macrophage polarization in RCC. In this study, cell apoptosis and proliferation were assessed by flow cytometry and CCK-8. Autolysosome fusion was observed by immunofluorescence detection of LC3 and LAMP2. The binding between HOXA3 and USP15 promoter was tested by ChIP, EMSA, and dual-luciferase reporter assays. Also, the interaction between deubiquitinated enzyme USP15 and SQSTM1, and ubiquitinated level of SQSTM1 were determined by Co-IP assay. Expression levels of HOXA3, USP15, CCL2, CCR2, M2-type macrophages and autophagy-related markers were measured by western blot, RT-qPCR, ELISA, and immunohistochemistry. Role of HOXA3/USP15 axis was verified by xenograft tumor experiment