RFWD2 increases proliferation and CDDP resistance of osteosarcoma cells

Abstract

P53, a key tumor suppressor gene, usually produces mtp53 proteins with oncogenic functions due to missense mutations in the DNA-binding domain. P53 is the most commonly mutated gene in osteosarcoma and plays an important role in the development and metastasis of osteosarcoma. The ubiquitin proteasome system is an evolutionarily conserved post-translational modification that regulates a variety of disease processes, including tumors. Researches have shown that RFWD2, as a function of an E3 ubiquitin ligase, plays an important role in regulating tumor progression. However, the biological function of RFWD2 in osteosarcoma cells with different p53 status remains to be clarified. Initially, we found that sarcoma patients with high levels of RFWD2 expression tended to have shorter overall survival time by analyzing UALCAN-TCGA data. Subsequently, we used CCK-8, colony formation, Transwell, and xenograft methods to confirm that RFWD2 acts as an oncogene, regulating the proliferation and invasion of osteosarcoma cells (HOS^(p53mut/-), U2OS^(p53wt/wt) and Saos-2^(p53-/-) cells) with different p53 status. Further co-IP experiments showed that in HOS^(p53mut/-) and U2OS^(p53wt/wt) cells, RFWD2 binds to p53 and participate in tumor progression. In addition, we demonstrated through both in vitro and in vivo experiments that RFWD2 regulates the sensitivity of osteosarcoma cells to CDDP. In conclusion, our study demonstrates that RFWD2 acts as an oncogene regulating osteosarcoma cell proliferation and sensitivity to CDDP. Our findings provide a new perspective and potential therapeutic target for the treatment of osteosarcoma.