Full text linksEuropean Review for Medical and Pharmacological Sciences TopBP1 promotes malignant progression and correlates with poor prognosis in osteosarcoma 1 Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People s Hospital, Shanghai, China. doctor_mindaliu@163.com. TopBP1 promotes malignant progression and correlates with poor prognosis in osteosarcoma 1 Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People s Hospital, Shanghai, China. doctor_mindaliu@163.com. Topoisomerase IIβ binding protein 1 (TopBP1) is involved in DNA damage and replication checkpoint and has been shown to be related to tumorigenesis in many cancer types. This study aimed to evaluate the biological role and clinicopathological significance of TopBP1 in OS. TopBP1 expression in sarcoma patients was determined through the Oncomine database, and the prognostic role of TopBP1 expression was assessed in a retrospective cohort study. CCK-8 assay and colony formation assay were employed to evaluate the effect of TopBP1 on proliferation and chemoresistance in OS cells. Cell apoptosis and cell cycle assay were used to assess the effect of TopBP1 on apoptosis and cycle of OS cells. We observed that TopBP1 expression was elevated not only in OS, but also in other sarcoma types including myxofibrosarcoma, liposarcoma, and leiomyosarcoma. Knockdown of TopBP1 using small interfering (si) RNA blocked cell proliferation and colony formation ability, and caused cell apoptosis as well as G1-phase arrest in OS cells. Moreover, TopBP1 knockdown decreased the chemoresistance of OS cells to both doxorubicin and cisplatin. Lastly, the retrospective cohort study showed that high TopBP1 expression was not only associated with high local recurrence and low necrosis rate, but also correlated with poor overall survival and disease-free survival of OS patients. Our findings indicate that TopBP1 contributes to the cell survival and chemoresistance to doxorubicin and cisplatin of OS, suggesting TopBP1 may serve as a novel target for inhibition of progression and chemotherapeutic resistance in OS patients. Lv Y, et al. Drug Des Devel Ther. 2016 Sep 23;10:3053-3064. doi: 10.2147/DDDT.S90705. eCollection 2016. Drug Des Devel Ther. 2016. PMID: 27729767 Free PMC article. Ma C, et al. Mol Med Rep. 2019 May;19(5):4205-4212. doi: 10.3892/mmr.2019.10104. Epub 2019 Mar 28. Mol Med Rep. 2019. PMID: 30942427 Free PMC article. Ma W, et al. Biochem Biophys Res Commun. 2020 Jan 1;521(1):204-211. doi: 10.1016/j.bbrc.2019.10.108. Epub 2019 Oct 19. Biochem Biophys Res Commun. 2020. PMID: 31640855 Asnafi AA, et al. Exp Mol Pathol. 2019 Feb;106:63-77. doi: 10.1016/j.yexmp.2018.12.002. Epub 2018 Dec 7. Exp Mol Pathol. 2019. PMID: 30528563 Liao YX, et al. Int J Oncol. 2019 Dec;55(6):1213-1222. doi: 10.3892/ijo.2019.4902. Epub 2019 Oct 18. Int J Oncol. 2019. PMID: 31638211 Free PMC article. Review. Wenmaekers S, Viergever BJ, Kumar G, Kranenburg O, Black PC, Daugaard M, Meijer RP. Wenmaekers S, et al. Cells. 2021 May 20;10(5):1262. doi: 10.3390/cells10051262. Cells. 2021. PMID: 34065298 Free PMC article. Review. Liu K, et al. J Biol Chem. 2021 Jan-Jun;296:100382. doi: 10.1016/j.jbc.2021.100382. Epub 2021 Feb 5. J Biol Chem. 2021. PMID: 33556369 Free PMC article.