Cui Wanmeng, Luo Wenqi, Zhou Xiaohui, Lu Yunliang, Xu Wenqing, Zhong Suhua, Feng Guofei, Liang Yushan, Liang Libin, Mo Yingxi, Xiao Xue, Huang Guangwu, Matskova Liudmila, Zhang Zhe, Li Ping, Zhou Xiaoying
Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Ministry of Education, Guangxi Medical University, Nanning, China.
Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning, China.
Front Oncol. 2019 Dec 17;9:1422. doi: 10.3389/fonc.2019.01422. eCollection 2019.
Kidney is an important organ for ketone body metabolism. However, the role of abnormal ketone metabolism and its possible function in tumorigenesis of clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. Three differentially expressed key enzymes involved in ketone body metabolism, ACAT1, BDH2, and HMGCL, were screened out between ccRCC and normal kidney tissues using the GEO and TCGA databases.We confirmed that the transcription and protein expression of ACAT1, BDH2, and HMGCL were significantly lower in ccRCC by real-time RT-PCR and IHC assays. Those patients with lower expression of these three genes have a worse outcome. In addition, we demonstrated that ectopic expression of each of these genes inhibited the proliferation of ccRCC cells. The overexpressed and genes remarkably impeded the migratory and invasive capacity of ccRCC cells. Furthermore, exogenous β-hydroxybutyrate suppressed the growth of ccRCC cells in a dose-dependent manner. Our findings suggest that , and are potential tumor suppressor genes, and constitute effective prognostic biomarkers for ccRCC. Ketone body metabolism might thus be a promising target in a process for developing novel therapeutic approaches to treat ccRCC.
肾脏是酮体代谢的重要器官。然而，异常酮代谢在肾透明细胞癌（ccRCC）肿瘤发生中的作用及其可能的功能尚未阐明。利用GEO和TCGA数据库，在ccRCC和正常肾组织之间筛选出了三种参与酮体代谢的差异表达关键酶，即ACAT1、BDH2和HMGCL。我们通过实时RT-PCR和免疫组化分析证实，ACAT1、BDH2和HMGCL在ccRCC中的转录和蛋白表达显著降低。这三个基因表达较低的患者预后较差。此外，我们证明这些基因中的每一个的异位表达均抑制ccRCC细胞的增殖。过表达的[此处原文可能缺失具体基因名称]基因显著阻碍了ccRCC细胞的迁移和侵袭能力。此外，外源性β-羟基丁酸以剂量依赖的方式抑制ccRCC细胞的生长。我们的研究结果表明，[此处原文可能缺失具体基因名称]是潜在的肿瘤抑制基因，并且构成ccRCC有效的预后生物标志物。因此，酮体代谢可能是开发治疗ccRCC新治疗方法过程中的一个有前景的靶点。
