Chen Zhaohui, Zhou Lijie, Wang Longwang, Kazobinka Gallina, Zhang Xiaoping, Han Xiaomin, Li Bin, Hou Teng
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Mol Carcinog. 2018 Jan;57(1):12-21. doi: 10.1002/mc.22715. Epub 2017 Sep 2.
Histone acetyltransferase binding to ORC1 (HBO1), a histone acetyltransferase, was recently identified as an oncoprotein; however, its role in bladder cancer remains unknown. In this study, we showed that HBO1 was highly expressed at both the mRNA and the protein levels in bladder cancer. HBO1 expression was associated with the clinical features of human bladder cancer, including tumor size (P = 0.018) and T (P = 0.007) classifications. Patients with higher HBO1 expression had shorter recurrence-free survival time, whereas patients with lower HBO1 expression had better survival time. Moreover, we found that ectopic overexpression of HBO1 promoted, whereas HBO1 silencing inhibited tumor growth in bladder cancer cells both in vitro and in vivo. We further demonstrated that upregulation of HBO1 activated the Wnt/β-catenin signaling pathway and led to nuclear localization of β-catenin and upregulation of downstream targets of of Wnt/β-catenin signaling. These findings suggest that HBO1 plays a key role in the progression of bladder cancer via the Wnt/β-catenin pathway, and may serve as a potential therapeutic target for the treatment of bladder cancer.
组蛋白乙酰转移酶与ORC1结合蛋白（HBO1）是一种组蛋白乙酰转移酶，最近被鉴定为一种癌蛋白；然而，其在膀胱癌中的作用尚不清楚。在本研究中，我们发现HBO1在膀胱癌的mRNA和蛋白水平均高表达。HBO1表达与人类膀胱癌的临床特征相关，包括肿瘤大小（P = 0.018）和T分期（P = 0.007）。HBO1表达较高的患者无复发生存时间较短，而HBO1表达较低的患者生存时间较好。此外，我们发现异位过表达HBO1可促进膀胱癌细胞的肿瘤生长，而沉默HBO1则在体外和体内均抑制肿瘤生长。我们进一步证明，HBO1的上调激活了Wnt/β-连环蛋白信号通路，导致β-连环蛋白的核定位以及Wnt/β-连环蛋白信号下游靶点的上调。这些发现表明，HBO1通过Wnt/β-连环蛋白途径在膀胱癌进展中起关键作用，并可能作为治疗膀胱癌的潜在治疗靶点。
