PTPN6 mediates the upregulation of THBS1 to promote M2-type macrophage polarization and the progression of renal cancer

Abstract The growing number of renal cancer cases annually underscores the importance of thorough research into its molecular mechanisms to achieve better outcomes. The purpose of this study was to assess how PTPN6 is expressed in various types of renal cancer and its connection to the immune microenvironment, as its role remains uncertain. Preliminary findings revealed that PTPN6 expression is considerably elevated in KIRC relative to normal controls. Elevated PTPN6 levels are also associated with a negative prognosis. A comprehensive review of the differentially expressed genes in KICH, KIRC, and KIRP revealed 55 common regulatory genes associated with immune responses. We hypothesized that PTPN6 plays a role in renal cancer development by regulating immune cell activity. In this study, mouse renal cell carcinoma cell lines with stable PTPN6 knockdown constructed using lentiviral vectors were cocultured with immune cells, and transcriptome sequencing was performed. PTPN6 knockdown significantly reduced THBS1 mRNA expression, as determined by quantitative reverse transcription polymerase chain reaction assay, which subsequently inhibited the M2 macrophage marker CD206+, as determined by flow cytometry. The research results will reveal the mechanism of PTPN6 in renal cell carcinoma and introduce new perspectives on immunotherapy methods