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DGAT2 通过下调细胞周期相关基因表达降低肝癌恶性程度。

Dgat2 reduces hepatocellular carcinoma malignancy via downregulation of cell cycle-related gene expression.

机构信息

Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, School of Medical Technology, Shanghai, 201318, China.

Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, School of Medical Technology, Shanghai, 201318, China; Shanghai Pudong Hospital Affiliated to Fudan University, China.

出版信息

Biomed Pharmacother. 2019 Jul;115:108950. doi: 10.1016/j.biopha.2019.108950. Epub 2019 May 8.

Abstract

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.

摘要

肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一,主要是因为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标,以便为这种毁灭性疾病制定新的治疗方法。在本研究中,我们证明与匹配的正常组织相比,二酰基甘油酰基转移酶 2(Dgat2)在人 HCC 组织中表达下调。此外,其高表达与更长的生存时间显著相关。此外,Dgat2 的过表达显著抑制 HCC 细胞的增殖。在体内研究中,我们发现当使用过表达 Dgat2 的 HCC 细胞时,源自 Balb/c 裸鼠的肿瘤的重量和体积明显减小。机制分析表明,Dgat2 过表达的 HCC 细胞中细胞周期相关基因的表达明显下调。总之,这些数据表明 Dgat2 是 HCC 细胞增殖的重要调节因子,可能代表 HCC 的潜在抗癌靶标和诊断生物标志物。

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