BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability  

作　　者：Xiaozhu Tang Mengjie guo Pinggang Ding Zhendong Deng Mengying Ke Yuxia Yuan Yanyan Zhou Zigen Lin Muxi Li Chunyan Gu Xiaosong Gu Ye Yang 

机构地区：[1]Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine,Nanjing,China [2]School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing,China [3]School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,China [4]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Nantong University,Nantong,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第11期3270-3282,共13页信号转导与靶向治疗（英文）

基　　金：This work was supported by National Key R&D Program of China(2020YFA0509400)(to Y.Y.);National Natural Science Foundation of China 81970196(to C.G.)and 82073885(to Y.Y.);Natural Science Foundation of Jiangsu Province BK20200097(to C.G.);Jiangsu Postgraduate Research and Practice Innovation Program KYCX20_1479(to X.T.)and KYCX21_1769(to R.W.).

摘　　要：Multiple myeloma(MM)is an incurable plasma cell malignancy in the bone marrow characterized by chromosome instability(CIN),which contributes to the acquisition of heterogeneity,along with MM progression,drug resistance,and relapse.In this study,we elucidated that the expression of BUB1B increased strikingly in MM patients and was closely correlated with poor outcomes.Overexpression of BUB1B facilitated cellular proliferation and induced drug resistance in vitro and in vivo,while genetic targeting BUB1B abrogated this effect.Mechanistic studies unveiled that enforced expression of BUB1B evoked CIN resulting in MM poor outcomes mainly through phosphorylating CEP170.Interestingly,we discovered the existence of circBUB1B_544aa containing the kinase catalytic center of BUB1B,which was translated by a circular RNA of BUB1B.The circBUB1B_544aa elevated in MM peripheral blood samples was closely associated with MM poor outcomes and played a synergistic effect with BUB1B on evoking CIN.In addition,MM cells could secrete circBUB1B_544aa and interfere the MM microenvironmental cells in the same manner as BUB1B full-length protein.Intriguingly,BUB1B siRNA,targeting the kinase catalytic center of both BUB1B and circBUB1B_544aa,significantly inhibited MM malignancy in vitro and in vivo.Collectively,BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets of MM.

关 键 词：MALIGNANCY inhibited MYELOMA 

分 类 号：R733.3[医药卫生—肿瘤]