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GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma
Chaofan Xie1,2, Wei Xiang2, Huiyong Shen3
1Department of Orthopaedic, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510000, Guangdong, People's Republic of China.
Background:
G2 and S phase-expressed-1 (GTSE1) negatively regulates the tumor-suppressive protein p53 and is potentially correlated with chemoresistance of cancer cells. This study aims to explore the effect of GTSE1 on the DNA damage repair and cisplatin (CDDP) resistance in osteosarcoma (OS).
Materials And Methods:
Expression of GTSE1 in OS was predicted in bioinformatics system GEPIA and then validated in clinically obtained tissues and acquired cell lines using RT-qPCR, immunohistochemical staining, and western blot assays. Gain- and loss-of-function studies of GTSE1 were performed in MG-63 and 143B cells to examine its function in cell cycle progression, DNA replication, and CDDP resistance. Stably transfected MG-63 cells were administrated into mice, followed by CDDP treatment to detect the role of GTSE1 in CDDP resistance in vivo.
Results:
GTSE1 was highly expressed in patients with OS and correlated with poor survival according to the bioinformatics predictions. Elevated GTSE1 expression was detected in OS tissues and cell lines. GTSE1 silencing reduced S/G2 transition and DNA replication, and it increased the CDDP sensitivity and decreased the expression of DNA repair-related biomarkers in MG-63 cells. GTSE1 overexpression in 143B cells led to inverse trends. In vivo, downregulation of GTSE1 strengthened the treating effect of CDDP and significantly repressed growth of xenograft tumors in nude mice. However, overexpression of GTSE1 blocked the anti-tumor effect of CDDP.
Conclusion:
This study demonstrates that GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in OS.
Insights
G2 and S phase-expressed-1 (GTSE1) promotes chemoresistance in osteosarcoma by affecting DNA repair. Silencing GTSE1 enhances cisplatin sensitivity and reduces tumor growth, suggesting GTSE1 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- G2 and S phase-expressed-1 (GTSE1) negatively regulates the tumor suppressor p53.
- GTSE1 is implicated in cancer cell chemoresistance.
- Osteosarcoma (OS) is a primary bone cancer with limited treatment options.
Purpose of the Study:
- To investigate the role of GTSE1 in DNA damage repair and cisplatin resistance in osteosarcoma.
- To determine the correlation between GTSE1 expression and patient survival in OS.
Main Methods:
- Bioinformatic analysis (GEPIA) and validation in clinical tissues/cell lines (RT-qPCR, IHC, Western blot).
- Gain- and loss-of-function studies in OS cells (MG-63, 143B) to assess effects on cell cycle, DNA replication, and cisplatin resistance.
- In vivo studies using xenograft mouse models to evaluate GTSE1's role in cisplatin resistance.
Main Results:
- GTSE1 is highly expressed in OS tissues and associated with poor survival.
- GTSE1 silencing in MG-63 cells reduced S/G2 transition, DNA replication, and increased cisplatin sensitivity.
- GTSE1 overexpression in 143B cells showed inverse effects.
- In vivo, GTSE1 downregulation enhanced cisplatin efficacy and repressed tumor growth; overexpression blocked anti-tumor effects.
Conclusions:
- GTSE1 plays a significant role in DNA damage repair and cisplatin resistance in osteosarcoma.
- GTSE1 is a potential therapeutic target for overcoming chemoresistance in OS.
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