Dgat2 reduces hepatocellular carcinoma malignancy via downregulation of cell cycle-related gene expression
Dgat2 reduces hepatocellular carcinoma malignancy via downregulation of cell cycle-related gene expression
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Dgat2 通过下调细胞周期相关基因表达来降低肝细胞癌的恶性程度
DOI：
10.1016/j.biopha.2019.108950
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发表时间：
2019-07-01
影响因子：
7.5
通讯作者：
Shen, Junwei
中科院分区：
文献类型：
--
作者：
Li, Yanfei;Li, Tingting;Shen, Junwei
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一，主要是由于缺乏有效的诊断生物标志物和治疗靶点。因此，迫切需要新的分子靶点，以便为这种毁灭性疾病制定新的治疗方法。在本研究中，我们证明了二酰基甘油酰基转移酶2（Dgat 2）在人肝癌组织中的下调与匹配的正常组织相比。此外，其高表达与较长的生存期显著相关。此外，Dgat 2过表达显著抑制HCC细胞增殖。在体内研究中，我们揭示了当使用过表达Dgat 2的HCC细胞时，来自Balb/c裸鼠的肿瘤的重量和体积显著降低。机制分析表明，细胞周期相关基因的表达显着下调，在肝癌细胞过表达Dgat 2。综上所述，这些数据表明Dgat 2是HCC细胞增殖的重要调节因子，并且可能代表HCC的潜在抗癌靶点和诊断生物标志物。
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, mainly due to the absence of effective diagnostic biomarkers and therapeutic targets. Therefore, novel molecular targets are urgently needed, in order to formulate novel therapeutic approaches for this devastating disease. In the present study, we demonstrated that diacylglycerol acyltransferase 2 (Dgat2) was downregulated in human HCC tissues compared with in matched normal tissues. Furthermore, its high expression was significantly associated with longer survival. In addition, Dgat2 overexpression significantly suppressed HCC cell proliferation. in vivo studies, we revealed that the weight and volume of the tumors derived from Balb/c nude mice was markedly decreased when using HCC cells overexpressing Dgat2. Mechanism analysis demonstrated that cell cycle-related gene expressions were significantly downregulated in HCC cells overexpressing Dgat2. Taken together, these data suggest that Dgat2 is an important regulator of HCC cell proliferation, and could represent a potential anticancer target and diagnostic biomarker for HCC.