Zhan Yuling, Dong Xiang, Yang Minghui, Li Suwan, Ou Mingrui, Wang Yuanyuan, Gao Yu
School of Life Science, Bengbu Medical University, 2600 Donghai Road, Bengbu, 233030, China.
Bengbu Medical University Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Bengbu Medical University, Bengbu, 233030, China.
Med Oncol. 2024 Sep 27;41(11):253. doi: 10.1007/s12032-024-02496-1.
Gamma-butyrobetaine hydroxylase (BBOX1) plays a pivotal role in catalyzing the final stage of L-carnitine biosynthesis. Recently, increasing number of studies have reported that BBOX1 is weakly expressed in tumor cells and exhibits antitumor activity. The role of BBOX1 in Hepatoblastoma (HB) has yet to be determined. To substantiate this, we have investigated BBOX1 expression and its clinical relevance in HB, and explored how BBOX1 might inhibit the occurrence and development of HB. The GSE104766 and GSE131329 datasets were used to screen for the core gene BBOX1 in HB and to analyze differences in expression between hepatoblastoma and normal tissues. Based on the clinicopathological features of the GSE131329 dataset, the connections between the expression of BBOX1 and the clinicopathological feature of HB patients were determined. After BBOX1 was overexpressed, CCK-8 and colony formation assays were employed to assess cell proliferation and wound healing experiments were utilized to assess cell migration. The presence of cell apoptosis, cell cycle changes, and reactive oxygen species (ROS) was assayed using flow cytometry. Compared with normal tissues, the expression of BBOX1 in hepatoblastoma tissues was notably decreased. Dysregulated expression of BBOX1 was indicated as a prognostic risk factor closely linked to clinical stag of patients with HB. Furthermore, following BBOX1 overexpression, cell proliferation and migration are decreased, the cell cycle is arrested, and ROS are attenuated. BBOX1 has suppressive effects on HepG2 cells, potentially through its ability to hinder cancer cell proliferation, arrest cell cycle progression, and decrease ROS levels, suggesting its potential as a novel prognostic biomarker and therapeutic candidate for hepatoblastoma.
γ-丁甜菜碱羟化酶（BBOX1）在催化左旋肉碱生物合成的最后阶段发挥着关键作用。最近，越来越多的研究报道BBOX1在肿瘤细胞中低表达并具有抗肿瘤活性。BBOX1在肝母细胞瘤（HB）中的作用尚未确定。为了证实这一点，我们研究了BBOX1在HB中的表达及其临床相关性，并探讨了BBOX1如何抑制HB的发生和发展。利用GSE104766和GSE131329数据集筛选HB中的核心基因BBOX1，并分析肝母细胞瘤与正常组织之间的表达差异。基于GSE131329数据集的临床病理特征，确定BBOX1表达与HB患者临床病理特征之间的联系。BBOX1过表达后，采用CCK-8和集落形成试验评估细胞增殖，采用伤口愈合试验评估细胞迁移。使用流式细胞术检测细胞凋亡、细胞周期变化和活性氧（ROS）的存在。与正常组织相比，肝母细胞瘤组织中BBOX1的表达明显降低。BBOX1表达失调被认为是与HB患者临床分期密切相关的预后危险因素。此外，BBOX1过表达后，细胞增殖和迁移减少，细胞周期停滞，ROS减弱。BBOX1对HepG2细胞具有抑制作用，可能是通过其阻碍癌细胞增殖、阻止细胞周期进程和降低ROS水平的能力实现的，这表明它有可能成为肝母细胞瘤的新型预后生物标志物和治疗候选物。
