Department of Orthopaedic, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510000, Guangdong, People's Republic of China.
Department of Orthopaedic, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, 518033, Guangdong, People's Republic of China.
J Orthop Surg Res. 2021 Dec 7;16(1):713. doi: 10.1186/s13018-021-02859-8.
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).
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.
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.
This study demonstrates that GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in OS.
G2 和 S 期表达蛋白 1（GTSE1）负调控抑癌蛋白 p53，与癌细胞的化疗耐药性可能相关。本研究旨在探讨 GTSE1 对骨肉瘤（OS）中 DNA 损伤修复和顺铂（CDDP）耐药性的影响。
在生物信息学系统 GEPIA 中预测 OS 中 GTSE1 的表达，然后使用 RT-qPCR、免疫组织化学染色和 Western blot 检测在临床获得的组织和获得的细胞系中验证 GTSE1 的表达。在 MG-63 和 143B 细胞中进行 GTSE1 的功能获得和功能丧失研究，以研究其在细胞周期进程、DNA 复制和 CDDP 耐药性中的作用。然后将稳定转染的 MG-63 细胞给予 CDDP 处理，以检测 GTSE1 在体内 CDDP 耐药性中的作用。
根据生物信息学预测，GTSE1 在 OS 患者中高表达，并与不良预后相关。在 OS 组织和细胞系中检测到 GTSE1 表达升高。GTSE1 沉默减少了 S/G2 转换和 DNA 复制，并增加了 MG-63 细胞的 CDDP 敏感性，降低了 DNA 修复相关生物标志物的表达。在 143B 细胞中过表达 GTSE1 则导致相反的趋势。体内研究中，下调 GTSE1 增强了 CDDP 的治疗效果，并显著抑制了裸鼠异种移植肿瘤的生长。然而，GTSE1 的过表达阻断了 CDDP 的抗肿瘤作用。
本研究表明 GTSE1 可能参与 OS 中的 DNA 损伤修复和顺铂耐药性。
