研究动态
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横纹肌动蛋白家族成员11通过OCT4途径促进了肝细胞癌的进展。

Kinesin family member 11 promotes progression of hepatocellular carcinoma via the OCT4 pathway.

发表日期:2023 Aug 30
作者: Ju Zhang, Zuxing Wei, Xiaoyan Qi, Yuhong Jiang, Dekun Liu, Kuijie Liu
来源: Cellular & Molecular Immunology

摘要:

肝细胞癌(HCC)是全球第二致死率最高的肿瘤。最近的研究数据显示,KIF11是肿瘤进展中的重要成员,属于动力蛋白家族(KIF)的一员。然而,其在HCC中的表达和分子机制尚不清楚。本研究评估了KIF11在HCC中的潜在作用。通过遗传或药物处理,在肝细胞癌细胞系LM3和Huh7上评估了KIF11的作用。使用其特异性抑制剂在异种移植动物模型中评估了KIF11的作用。通过从上述动植物模型获取的标本,在多种体内外实验后系统评估了KIF11的作用。临床病理分析表明,KIF11在肝细胞癌患者中高表达。体外细胞实验显示,KIF11缺乏显著减慢了肝肿瘤细胞的增殖。在过表达OCT4的肝癌细胞实验中,与仅KIF11基因沉默的肿瘤细胞相比,OCT4的过表达显著增加了肿瘤细胞的增殖。体外细胞实验和体内异种移植瘤实验均显示,KIF11的抑制剂单麻醉剂可有效延缓肿瘤细胞的增殖和迁移。基于这些结果,KIF11在肝细胞癌中表达高,并以OCT4依赖的方式促进肿瘤增殖。KIF11可能成为肝细胞癌的治疗靶点,其抑制剂单麻醉剂可能成为临床抗肿瘤药物。© 2023. 作者(s)独家许可给微软公司,微软公司属于微软自然部门。
Hepatocellular carcinoma (HCC) is the tumor with the second highest mortality rate worldwide. Recent research data show that KIF11, a member of the kinesin family (KIF), plays an important role in the progression of various tumors. However, its expression and molecular mechanism in HCC remain elusive. Here, we evaluated the potential role of KIF11 in HCC. The effect of KIF11 was evaluated using the hepatocellular carcinoma cell lines, LM3 and Huh7, after genetic or pharmacological treatment. Evaluating the role of KIF11 in the xenograft animal models using its specific inhibitor. The role of KIF11 was systematically evaluated using specimens obtained from the aforementioned animal and cell models after various in vivo and in vitro experiments. The clinicopathological analysis showed that KIF11 was expressed at high levels in patients with hepatocellular carcinoma. Cell experiments in vitro showed that KIF11 deficiency significantly slowed the proliferation of liver tumor cells. And in the experiment using liver cancer cells overexpressing OCT4, overexpression of OCT4 substantially increased the proliferation of tumor cells compared with tumor cells with KIF11 knockdown alone. Both in vitro cell experiment and in vivo xenotransplantation tumor experiment showed that monastrol, an inhibitor of KIF11, could effectively delay the proliferation and migration of tumor cells. Based on these results, KIF11 is expressed at high levels in hepatocellular carcinoma and promotes tumor proliferation in an OCT4-dependent manner. KIF11 may become a therapeutic target for hepatocellular carcinoma, and its inhibitor monastrol may become a clinical antitumor drug.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.