SIRPB1 is transcriptionally regulated by USF2 and promotes cutaneous malignant melanoma tumorigenicity through SOCS1/STAT3 signaling

Melanocyte-derived cutaneous malignant melanoma (MM) is the most common malignant skin cancer and the leading cause of skin cancer-related deaths. The role of SIRPB1 in cutaneous MM pathogenesis remains unknown, despite its established involvement in tumorigenesis. This study aimed to investigate its function and underlying mechanisms in cutaneous MM. We demonstrated that SIRPB1 downregulation suppresses cutaneous melanoma cell proliferation, migration, and invasion both in vitro and vivo. Mechanistically, SIRPB1 knockdown upregulated SOCS1, a negative regulator of STAT3 signaling. Moreover, a STAT3 agonist reversed the tumor-suppressive effects of SIRPB1 knockdown. We further identified USF2 as a transcriptional activator that binds to the SIRPB1 promoter. By elucidating the molecular mechanism of SIRPB1 in MM progression, we found that SIRPB1 is the oncogenic gene for cutaneous MM. Mechanistically, SIRPB1 is transcriptionally regulated by USF2 and promotes tumorigenesis via the SOCS1/STAT3 pathway, highlighting the therapeutic potential of targeting the USF2/SIRPB1 axis.