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

Journal of Orthopaedic Surgery and Research

Jingnan Shen¹  Wei Xiang²  Huiyong Shen²  Chaofan Xie³ 

[1]Department of Muscularskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, 510000, Guangzhou, Guangdong, People’s Republic of China

[2]Department of Orthopaedic, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, 518033, Shenzhen, Guangdong, People’s Republic of China

[3]Department of Orthopaedic, The First Affiliated Hospital of Sun Yat-Sen University, 510000, Guangzhou, Guangdong, People’s Republic of China

[4]Department of Orthopaedic, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, 518033, Shenzhen, Guangdong, People’s Republic of China

关键词: Osteosarcoma;    GTSE1;    DNA repair;    Cisplatin;    Drug resistance;   

DOI  :  10.1186/s13018-021-02859-8

来源: Springer

【 摘 要 】

BackgroundG2 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 methodsExpression 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.ResultsGTSE1 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.ConclusionThis study demonstrates that GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in OS.

【 授权许可】

CC BY