TRIM56 Reduces Radiosensitization of Human Glioblastoma by Regulating FOXM1-Mediated DNA Repair.

Abstract

Recurrent glioblastoma is characterized by resistance to radiotherapy or chemotherapy. In this study, we investigated the role of TRIM56 in radiosensitization and its potential underlying molecular mechanism. TRIM56 expression levels were measured in glioblastoma tissues and cell lines by immunohistochemical staining, western blot, and qRT-PCR. MTT assay, colony formation assay, and TUNEL assay were used to investigate the effect of TRIM56 on cell viability, cell proliferation, and cell apoptosis. Co-immunoprecipitation was used to clarify the interaction between TRIM56 and FOXM1. Finally, tumor xenograft experiments were performed to analyze the effect of TRIM56 on tumor growth in vivo. The expression of TRIM56 was significantly increased in glioblastoma tissues and cell lines and its expression was associated with poor prognosis of patients with glioblastoma. Moreover, TRIM56 reduced the radiosensitivity of glioblastoma cells and promoted DNA repairment. Mechanistically, TRIM56 promoted FOXM1 protein level, enhanced the stability of FOXM1 by de-ubiquitination, and promoted DNA damage repair through FOXM1 in glioblastoma cells. TRIM56 could reduce the radiosensitivity of glioblastoma in vivo. TRIM56 may suppress the radiosensitization of human glioblastoma by regulating FOXM1-mediated DNA repair. Targeting the TRIM56 may be an effective method to reverse radiotherapy-resistant in glioblastoma recurrent.