DOI: 10.1002/ame2.12370
Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc
Ke Liu1
Xuxuan Zhou2
Fei Huang1
Lihao Liu3
Zijian Xu3
Chongqing Gao2
Keke Zhang2
Jian Hong2
Nan Yao2
Guohua Cheng1
1.College of Pharmacy,Jinan University,Guangzhou,China2.Department of Pathophysiology,School of Medicine,Jinan University,Guangzhou,China3.School of Medicine,Jinan University,Guangzhou,China
摘要：Background:Cholangiocarcinoma(CCA),a malignancy that arises from biliary epithe-lial cells,has a dismal prognosis,and few targeted therapies are available.Aurora B,a key mitotic regulator,has been reported to be involved in the progression of various tumors,yet its role in CCA is still unclarified.
Methods:Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA.A loss-of-function model was constructed in CCA cells to determine the role of Aurora B in CCA progression.Subcutaneous and liver orthotopic xenograft models were used to assess the therapeutic potential of Aurora B inhibitors in CCA.
Results:In murine spontaneous CCA models,Aurora B was significantly upregu-lated.Elevated Aurora B expression was also observed in 62.3％of human speci-mens in our validation cohort(143 CCA specimens),and high Aurora B expression was positively correlated with pathological parameters of tumors and poor sur-vival.Knockdown of Aurora B by siRNA and heteroduplex oligonucleotide(HDO)or an Aurora B kinase inhibitor(AZD1152)significantly suppressed CCA progres-sion via G2/M arrest induction.An interaction between Aurora B and c-Myc was found in CCA cells.Targeting Aurora B significantly reduced this interaction and accelerated the proteasomal degradation of c-Myc,suggesting that Aurora B pro-moted the malignant properties of CCA by stabilizing c-Myc.Furthermore,sequen-tial application of AZD1152 or Aurora B HDO drastically improved the efficacy of gemcitabine in CCA.
Conclusions:Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA.
机标关键词：auroracholocarolancarcinomafacilitatesprogressionstabilizing
论文发表日期：2024-10-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 626-640 )
英文信息