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TRIM4 Expression Related to Malignant Progression and Cisplatin Resistance in Osteosarcoma
1Department of Joint Surgery, Shandong Second Provincial General Hospital, No.4 Duanxing West Road, Huaiyin District, Jinan, 250022, People's Republic of China.
Abstract:
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.
Insights
High TRIM4 expression correlates with poor outcomes in osteosarcoma (OS). Targeting TRIM4 may improve chemotherapy sensitivity and reduce malignant progression in OS patients resistant to standard treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a primary bone cancer with a significant portion of patients exhibiting resistance to standard chemotherapy.
- Identifying molecular mechanisms underlying chemotherapy resistance is crucial for improving OS patient outcomes.
Purpose of the Study:
- To investigate the role of TRIM4 in osteosarcoma (OS) chemotherapy sensitivity and malignant progression.
- To explore TRIM4 as a potential therapeutic target for overcoming treatment resistance in OS.
Main Methods:
- Examined TRIM4 expression in OS tissues and cell lines using RT-qPCR, immunohistochemistry, and Western blot.
- Utilized siRNA to knockdown TRIM4 in OS cells (U2-OS, SAOS2) and assessed cell proliferation, migration, invasion, and apoptosis.
- Established cisplatin-resistant SAOS2 cells (SAOS2-Cis-R) to evaluate TRIM4's impact on cisplatin response.
Main Results:
- TRIM4 knockdown significantly inhibited OS cell proliferation, migration, and invasion, while inducing apoptosis.
- TRIM4 expression was notably higher in chemotherapy-resistant OS tissues and cisplatin-resistant SAOS2 cells compared to sensitive counterparts.
- TRIM4 overexpression conferred cisplatin resistance, whereas TRIM4 downregulation enhanced cisplatin sensitivity in resistant OS cells.
Conclusions:
- Elevated TRIM4 expression is associated with osteosarcoma (OS) progression and resistance to chemotherapy.
- Targeting TRIM4 presents a promising strategy for enhancing the efficacy of chemotherapy and combination therapies in OS treatment.
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