BDH2 is downregulated in hepatocellular carcinoma and acts as a tumor suppressor regulating cell apoptosis and autophagy
BDH2 is downregulated in hepatocellular carcinoma and acts as a tumor suppressor regulating cell apoptosis and autophagy
复制标题
BDH2 在肝细胞癌中下调，并作为肿瘤抑制因子调节细胞凋亡和自噬
DOI：
10.7150/jca.32022
复制
发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Deng, Meihai
中科院分区：
文献类型：
--
作者：
Liang, Hao;Xiong, Zhiyong;Deng, Meihai
BDH 2是短链脱氢酶/还原酶家族成员，参与多种生物学和病理学过程，包括细胞溶质酮体的利用、免疫细胞调节和肿瘤进展。在这项研究中，我们首先通过qRT-PCR和免疫组化分析揭示了BHD 2在HCC组织中下调，并且低BHD 2表达与总体生存率差、肿瘤分化差、肿瘤大小增加、静脉浸润和晚期BCLC分期显著相关。单因素和多因素分析结果表明，BDH 2可能是一个独立的预后指标。BDH 2作为酮代谢相关基因家族的一员，可上调肝细胞β-HB水平和H3组蛋白乙酰化水平。功能分析表明，BDH 2表达抑制肿瘤细胞的生长，增殖和迁移。机制分析结果表明，BDH 2通过未折叠蛋白反应诱导线粒体凋亡并抑制自噬。因此，BDH 2可能是一个新的肝癌预后标志物和有用的治疗靶点。
BDH2 is a short-chain dehydrogenase/reductase family member involved in several biological and pathological processes, including the utilization of cytosolic ketone bodies, immunocyte regulation and tumor progression. In this study, we first revealed that BDH2 was downregulated in HCC tissues by qRT-PCR and immunohistochemistry analysis and that low BHD2 expression was significantly associated with poor overall survival, poor tumor differentiation, increased tumor size, venous invasion and an advanced BCLC stage. Moreover, the results of a univariate analysis and multivariate analysis revealed that BDH2 may be regarded as an independent prognostic marker. As a member of a gene family involved in ketone metabolism, BDH2 upregulated the level of β-HB in liver cells as well as the level of H3 histone acetylation. Functional analysis showed that BDH2 expression inhibited tumor cell growth, proliferation and migration. The results of the mechanistic analysis revealed that BDH2 induced mitochondrial apoptosis and inhibited autophagy through the unfolded protein response. Therefore, BDH2 may be a new HCC prognostic marker and a useful treatment target.