Glioblastoma multiforme(GBM)is the deadliest form of brain tumor,and effective treatments are lacking.Thus,a new generation of effective treatments is urgently needed.B-cell lymphoma 6(BCL6)is a transcription factor t...Glioblastoma multiforme(GBM)is the deadliest form of brain tumor,and effective treatments are lacking.Thus,a new generation of effective treatments is urgently needed.B-cell lymphoma 6(BCL6)is a transcription factor that functions to suppress the transcription of DNA damage response genes,halting cell death in response to DNA damage.Here,we identified BCL6 as a lynchpin in GBM,the expression of which was greater in GBM cells than in normal cells and associated with poor survival in GBM patients.The silencing of BCL6 additionally affected GBM cell proliferation and triggered cellular damage.Furthermore,we reported the identification of YK01,a novel small-molecule inhibitor of BCL6.YK01 exhibited excellent anti-GBM bioactivity and caused apoptosis;importantly,YK01 significantly inhibited the growth of GBM cells both in vitro and in vivo.Moreover,the combination of YK01 and temozolomide treatment significantly suppressed the growth and metastasis of tumors in vivo and prolonged the survival of mice with tumors.In summary,our findings reveal that BCL6 appears to play a crucial role in GBM and may be a therapeutic target for treating this incurable condition.展开更多
基金supported by the grants from the National Natural Science Foundation of China(No.82073310,82373146,82202897)The Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital(China)(No.PI202430)+3 种基金Shanghai Rising-Star Program(No.23QB1405600)The Science and Technology Commission of Shanghai Municipality,China(No.22QB1405600)Biomedical Projects of Yunnan Key Science and Technology Program(202502AA310002)ECNU(East China Normal University)Construction Fund of Innovation and Entrepreneurship Laboratory(Shanghai,China)(No.44400-20201-532300/021).
文摘Glioblastoma multiforme(GBM)is the deadliest form of brain tumor,and effective treatments are lacking.Thus,a new generation of effective treatments is urgently needed.B-cell lymphoma 6(BCL6)is a transcription factor that functions to suppress the transcription of DNA damage response genes,halting cell death in response to DNA damage.Here,we identified BCL6 as a lynchpin in GBM,the expression of which was greater in GBM cells than in normal cells and associated with poor survival in GBM patients.The silencing of BCL6 additionally affected GBM cell proliferation and triggered cellular damage.Furthermore,we reported the identification of YK01,a novel small-molecule inhibitor of BCL6.YK01 exhibited excellent anti-GBM bioactivity and caused apoptosis;importantly,YK01 significantly inhibited the growth of GBM cells both in vitro and in vivo.Moreover,the combination of YK01 and temozolomide treatment significantly suppressed the growth and metastasis of tumors in vivo and prolonged the survival of mice with tumors.In summary,our findings reveal that BCL6 appears to play a crucial role in GBM and may be a therapeutic target for treating this incurable condition.
