TopBP1 promotes malignant progression and correlates with poor prognosis in osteosarcoma

OBJECTIVE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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