Zhang Zehua, Dai Fei, Luo Fei, Wu Wenjie, Zhang Shuai, Zhou Rui, Xu Jianzhong, Zhou Qiang, Song Lei
Department of Orthopaedics, First Affiliated Hospital, Army Medical University, No. 30 Gaotanyanzheng street, Chongqing, 400038, China.
Department of Orthopaedics, Third Affiliated Hospital, Medical University of Chongqing, Chongqing,, 401120, China.
Discov Oncol. 2021 Jul 1;12(1):20. doi: 10.1007/s12672-021-00415-8.
Osteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.
骨肉瘤是一种恶性成骨肿瘤,会严重危及儿童和青少年的生命健康。因此,迫切需要探索骨肉瘤的新生物标志物,并确定新的靶向治疗方法,以提高骨肉瘤的治疗效果。Diaphanous相关成膜蛋白3(DIAPH3)促进肝细胞癌和肺腺癌的肿瘤发生,这表明DIAPH3可能是肿瘤治疗的一个靶点。迄今为止,尚无关于DIAPH3在骨肉瘤中功能的报道。通过免疫组织化学染色检测骨肉瘤组织及癌细胞旁健康骨组织中DIAPH3蛋白的表达。DIAPH3 mRNA表达与总生存期和无病生存期缩短相关。DIAPH3蛋白在骨肉瘤组织中上调及其表达与肿瘤大小、肿瘤分期、淋巴结转移和远处转移显著相关。体外功能实验表明,敲低DIAPH3可抑制骨肉瘤细胞系MG-63和HOS的细胞增殖、迁移和侵袭。功能实验证明,敲低DIAPH3可抑制体内皮下肿瘤生长和肺转移。总之,DIAPH3表达可预测骨肉瘤的临床结局。此外,DIAPH3参与骨肉瘤的增殖和转移,因此,DIAPH3可能是骨肉瘤的一个潜在治疗靶点。