GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma

被引:16
作者
Xie, Chaofan [1 ,2 ]
Xiang, Wei [2 ]
Shen, Huiyong [2 ]
Shen, Jingnan [3 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Orthopaed, Guangzhou 510000, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Orthopaed, 3025 Shennan Middle Rd, Shenzhen 518033, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Muscularskeletal Oncol, 58,Zhongshan 2nd Rd, Guangzhou 510000, Guangdong, Peoples R China
关键词
Osteosarcoma; GTSE1; DNA repair; Cisplatin; Drug resistance; NONSMALL CELL; IDENTIFICATION; PROTEIN; CANCER;
D O I
10.1186/s13018-021-02859-8
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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.
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页数:11
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