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NEDD4 promotes cell growth and motility in hepatocellular carcinoma

机译：NEDD4促进肝细胞癌中的细胞生长和运动性

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摘要

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In China, the situation is even worse as cancer incidence and mortality continue to increase rapidly. Although tremendous progress has been made toward HCC treatments, the benefits for liver cancer patients are still limited. Therefore, it is necessary to identify and develop novel therapeutic methods. Neuronally expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, plays a critical role in the development and progression of various types of human cancers. In our study, NEDD4 acts as an oncoprotein in both QGY7703 and SMMC7721 liver cancer cell lines. We found that depletion of NEDD4 by siRNA transfection led to inhibition of cell growth, invasion and migration, and promotion of apoptosis. In contrast, overexpression of NEDD4 via plasmid transfection resulted in facilitated cell proliferation, invasion and migration, and decreased apoptosis. Importantly, we observed that tumor suppressor LATS1, also a core component of Hippo pathway, was negatively regulated by NEDD4 in liver cancer cells. Our findings suggested that NEDD4 may be involved in the HCC progression via regulating LATS1 associated signaling pathway. Therefore, targeting NEDD4-LATS1 signaling could be a potential therapeutic option for HCC treatment.
机译：肝细胞癌（HCC）是全世界癌症相关死亡最常见的原因之一。在中国，随着癌症发病率和死亡率迅速增加，情况甚至更糟糕。虽然对HCC治疗进行了巨大进展，但肝癌患者的益处仍然有限。因此，有必要识别和开发新的治疗方法。神经大致表达的发育下调4（NEDD4），一种E3泛素连接酶，在各种类型人类癌症的发展和进展中起着关键作用。在我们的研究中，NEDD4在QGY7703和SMMC7721肝癌细胞系中作为癌蛋白。我们发现SiRNA转染的NEDD4的耗尽导致抑制细胞生长，侵袭和迁移以及促进细胞凋亡。相反，通过质粒转染的NEDD4的过度表达导致促进细胞增殖，侵袭和迁移，降低细胞凋亡。重要的是，我们观察到肿瘤抑制剂LATS1，也是河马途径的核心成分，对肝癌细胞中的NEDD4负调节。我们的研究结果表明，NEDD4可以通过调节LATS1相关的信号通路参与HCC进展。因此，靶向NEDD4-LATS1信号传导可能是HCC处理的潜在治疗选择。

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  • 来源
    《Cell cycle》 |2018年第6期|共11页
  • 作者

    Zheng Hailun; Ke Xiquan; Li Dapeng; Wang Qiangwu; Wang Jianchao; Liu Xiaoyang; Deng Min; Deng Xiaojing; Xue Yongju; Zhu Yu; Wang Qizhi;

  • 作者单位

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

    Bengbu Med Coll Affiliated Hosp 1 Dept Gastroenterol Bengbu 233004 Anhui Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Hepatocellular carcinoma (HCC); NEDD4; LATS1;

    机译：肝细胞癌（HCC）;NEDD4;LATS1;

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