Department of Joint Surgery, Shandong Second Provincial General Hospital, No.4 Duanxing West Road, Huaiyin District, Jinan, 250022, People's Republic of China.
Appl Biochem Biotechnol. 2024 Jan;196(1):233-244. doi: 10.1007/s12010-023-04551-5. Epub 2023 Apr 28.
Osteosarcoma (OS) is a high-grade intraosseous malignancy. Twenty to thirty percent of OS patients react poorly to standard therapy with a combination of surgical resection and chemotherapy. It is necessary to find molecules that play an important role in this. This study explored the role of TRIM4 in OS chemotherapy sensitivity and malignant progression. The expression of TRIM4 in OS tissues and cells was examined by RT-qPCR, immunohistochemical staining, and western blot. Specific siRNA was transfected into U2-OS and SAOS2 cells to target TRIM4. Cell biological behavior was examined by CCK-8, Transwell, and flow cytometry experiments. Cisplatin-resistant SAOS2 (SAOS2-Cis-R) cells were established, and the effect of TRIM4 expression on the cisplatin response of SAOS2 cells was tested. Knockdown of TRIM4 significantly inhibited the proliferation, migration, and invasion of U2-OS and SAOS2 cells and induced apoptosis. TRIM4 expression was significantly higher in chemotherapy-resistant OS tissues compared to chemotherapy-sensitive OS tissues. Furthermore, the expression of TRIM4 in SAOS2-Cis-R cells was significantly increased compared to parental SAOS2 cells. Moreover, overexpression of TRIM4 enhanced cisplatin resistance in parental SAOS2 cells, while the downregulation of TRIM4 expression enhanced cisplatin sensitivity of SAOS2-Cis-R cells. High TRIM4 expression might be associated with malignant progression and poor response to chemotherapy response of OS. Targeting TRIM4 may be beneficial for OS treatment or combination therapy.
骨肉瘤(OS)是一种高级的骨内恶性肿瘤。20%到 30%的骨肉瘤患者对手术切除和化疗相结合的标准治疗反应不佳。因此,有必要寻找在这方面发挥重要作用的分子。本研究探讨了 TRIM4 在骨肉瘤化疗敏感性和恶性进展中的作用。通过 RT-qPCR、免疫组织化学染色和 Western blot 检测 TRIM4 在骨肉瘤组织和细胞中的表达。通过特异性 siRNA 转染 U2-OS 和 SAOS2 细胞靶向 TRIM4。通过 CCK-8、Transwell 和流式细胞术实验检测细胞生物学行为。建立了顺铂耐药的 SAOS2(SAOS2-Cis-R)细胞,并检测了 TRIM4 表达对 SAOS2 细胞对顺铂反应的影响。TRIM4 敲低显著抑制了 U2-OS 和 SAOS2 细胞的增殖、迁移和侵袭,并诱导了细胞凋亡。与化疗敏感的骨肉瘤组织相比,化疗耐药的骨肉瘤组织中 TRIM4 的表达明显升高。此外,SAOS2-Cis-R 细胞中 TRIM4 的表达明显高于亲本 SAOS2 细胞。此外,TRIM4 的过表达增强了亲本 SAOS2 细胞对顺铂的耐药性,而 TRIM4 表达的下调增强了 SAOS2-Cis-R 细胞对顺铂的敏感性。高 TRIM4 表达可能与骨肉瘤的恶性进展和对化疗反应不佳有关。靶向 TRIM4 可能有助于骨肉瘤的治疗或联合治疗。