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HRD1 的上调促进了结肠癌的细胞迁移和侵袭。

Upregulation of HRD1 promotes cell migration and invasion in colon cancer.

机构信息

Department of Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou St., Nanjing, 210029, Jiangsu, People's Republic of China.

Department of Digestive Endoscopy Center, Zhongda Hospital Southest University, Nanjing, 210009, Jiangsu, People's Republic of China.

出版信息

Mol Cell Biochem. 2019 Apr;454(1-2):1-9. doi: 10.1007/s11010-018-3447-0. Epub 2018 Oct 10.

Abstract

3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) is an E3 ubiquitin ligase that functions by promoting degradation of misfolded proteins in processes such as embryogenesis and rheumatoid arthritis. However, little is known about the role of HRD1 in cancer. The aim of the present study was to investigate the expression pattern and functions of HRD1 in human colon cancer (CC). We found that HRD1 expression was increased significantly in human CC tissues, and its overexpression was associated with TNM stage, tumor differentiation, tumor invasive depth, and distant metastasis. Knockdown of HRD1 using small hairpin (sh) RNA plasmid significantly inhibited CC cell migration and invasion. Furthermore, the silencing of HRD1 decreased the expression of MMP-2 and MMP-9, which is critical for CC cell migration and invasion. Taken together, these results revealed that HRD1 is overexpressed in CC and promotes migration and invasion of CC cells. Inhibition of HRD1 may be considered as an effective anti-CC strategy.

摘要

3-羟-3-甲基戊二酰基辅酶 A 还原酶降解(HRD1)是一种 E3 泛素连接酶,通过促进发育和类风湿性关节炎等过程中错误折叠蛋白的降解来发挥作用。然而,关于 HRD1 在癌症中的作用知之甚少。本研究旨在探讨 HRD1 在人结肠癌(CC)中的表达模式和功能。我们发现 HRD1 在人 CC 组织中的表达显著增加,其过表达与 TNM 分期、肿瘤分化、肿瘤侵袭深度和远处转移有关。使用短发夹(sh)RNA 质粒敲低 HRD1 显著抑制了 CC 细胞的迁移和侵袭。此外,HRD1 的沉默降低了对 CC 细胞迁移和侵袭至关重要的 MMP-2 和 MMP-9 的表达。总之,这些结果表明 HRD1 在 CC 中过表达,并促进 CC 细胞的迁移和侵袭。抑制 HRD1 可能被认为是一种有效的抗 CC 策略。

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