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 malignancy of the skin and the leading cause of skin cancer-related deaths worldwide. Although SIRPB1 is involved in tumorigenesis and development in various cancers, its role in cutaneous MM is still not elucidated. Our work investigates the role of SIRPB1 in the pathogenesis of cutaneous MM and explores its specific function mechanism. SIRPB1 downregulation inhibited the proliferation, migration, and invasion of melanoma cells, both <i>in vitro</i> and <i>in vivo</i>. SIRPB1 knockdown could significantly upregulate SOSC1 expression in melanoma cells, negatively regulating STAT3. STAT3 agonists reversed the SIRPB1 gene knockdown-induced tumor inhibition. USF2 played a transcriptional regulatory role by binding to the SIRPB1 promoter sequence. SIRPB1 is an oncogene of cutaneous MM, transcriptionally regulated by USF2. It promotes cutaneous MM tumorigenicity by regulating the SOCS1/STAT3 signaling. Hence, the targeted regulation of SIRPB1 and USF2 could be a promising therapeutic strategy for MM.