Department of Health Management Center, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, China.
Department of Pediatrics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, China.
Gene. 2025 Jan 15;933:148973. doi: 10.1016/j.gene.2024.148973. Epub 2024 Sep 28.
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, U2OS and Saos-2 cells) with different p53 status. Further co-IP experiments showed that in HOS and U2OS 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.
p53 是一种关键的肿瘤抑制基因，通常由于 DNA 结合域的错义突变产生具有致癌功能的 mtp53 蛋白。p53 是骨肉瘤中最常见的突变基因，在骨肉瘤的发生和转移中发挥重要作用。泛素蛋白酶体系统是一种进化上保守的翻译后修饰，调节多种疾病过程，包括肿瘤。研究表明，RFWD2 作为一种 E3 泛素连接酶的功能，在调节肿瘤进展中起着重要作用。然而，RFWD2 在不同 p53 状态的骨肉瘤细胞中的生物学功能仍有待阐明。最初，我们通过分析 UALCAN-TCGA 数据发现，RFWD2 表达水平高的肉瘤患者总体生存时间往往较短。随后，我们使用 CCK-8、集落形成、Transwell 和异种移植方法证实，RFWD2 作为一种癌基因，调节不同 p53 状态的骨肉瘤细胞（HOS、U2OS 和 Saos-2 细胞）的增殖和侵袭。进一步的 co-IP 实验表明，在 HOS 和 U2OS 细胞中，RFWD2 与 p53 结合并参与肿瘤进展。此外，我们通过体外和体内实验证明，RFWD2 调节骨肉瘤细胞对 CDDP 的敏感性。总之，我们的研究表明，RFWD2 作为一种癌基因调节骨肉瘤细胞的增殖和对 CDDP 的敏感性。我们的研究结果为骨肉瘤的治疗提供了新的视角和潜在的治疗靶点。
