GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma
Abstract 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 (O...
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Format: | Article |
Language: | English |
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BMC
2021-12-01
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Series: | Journal of Orthopaedic Surgery and Research |
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Online Access: | https://doi.org/10.1186/s13018-021-02859-8 |
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author | Chaofan Xie Wei Xiang Huiyong Shen Jingnan Shen |
author_facet | Chaofan Xie Wei Xiang Huiyong Shen Jingnan Shen |
author_sort | Chaofan Xie |
collection | DOAJ |
description | Abstract 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. |
first_indexed | 2024-04-13T08:23:10Z |
format | Article |
id | doaj.art-10f52db25cf94fd38ff4bb6f9b91feec |
institution | Directory Open Access Journal |
issn | 1749-799X |
language | English |
last_indexed | 2024-04-13T08:23:10Z |
publishDate | 2021-12-01 |
publisher | BMC |
record_format | Article |
series | Journal of Orthopaedic Surgery and Research |
spelling | doaj.art-10f52db25cf94fd38ff4bb6f9b91feec2022-12-22T02:54:33ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-12-0116111110.1186/s13018-021-02859-8GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcomaChaofan Xie0Wei Xiang1Huiyong Shen2Jingnan Shen3Department of Orthopaedic, The First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Orthopaedic, The Eighth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Orthopaedic, The Eighth Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Muscularskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen UniversityAbstract 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.https://doi.org/10.1186/s13018-021-02859-8OsteosarcomaGTSE1DNA repairCisplatinDrug resistance |
spellingShingle | Chaofan Xie Wei Xiang Huiyong Shen Jingnan Shen GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma Journal of Orthopaedic Surgery and Research Osteosarcoma GTSE1 DNA repair Cisplatin Drug resistance |
title | GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma |
title_full | GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma |
title_fullStr | GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma |
title_full_unstemmed | GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma |
title_short | GTSE1 is possibly involved in the DNA damage repair and cisplatin resistance in osteosarcoma |
title_sort | gtse1 is possibly involved in the dna damage repair and cisplatin resistance in osteosarcoma |
topic | Osteosarcoma GTSE1 DNA repair Cisplatin Drug resistance |
url | https://doi.org/10.1186/s13018-021-02859-8 |
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