PCMTD1-127aa suppresses osteosarcoma progression by competitively binding to USP10 to promote c-MYC degradation

Osteosarcoma (OS) is a highly malignant tumor prone to distant metastasis and is associated with a poor prognosis. To date, therapeutic outcomes for this disease remain unsatisfactory. In this study, we found that circPCMTD1 encodes a 127-amino acid protein, termed PCMTD1-127aa in OS. The expression of PCMTD1-127aa was significantly lower in OS tissues than in normal paratumoral tissues. Clinical data analysis revealed that low expression of PCMTD1-127aa was associated with poor OS prognosis. Functionally, overexpression of PCMTD1-127aa not only inhibited the proliferation and invasion of osteosarcoma cells but also suppressed glycolysis in these cells. Mechanistically, PCMTD1-127aa competitively bound to the F1 (1-100) domain of USP10, thereby counteracting the USP10-mediated deubiquitination of c-MYC and subsequently promoting c-MYC degradation. We further identified that amino acid 148 of c-MYC plays a critical role in ubiquitination-mediated degradation. Our findings reveal the PCMTD1-127aa/USP10/c-MYC axis may be a promising therapeutic target for OS.