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The role and mechanism of action of RNF186 in colorectal cancer through negative regulation of NF-kappa B

机译：RNF186在结直肠癌中的作用和机制通过NF-Kappa B的阴性调节

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摘要

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers worldwide. RING finger protein 186 (RNF186) is a member of the RING finger protein family. RNF186 has been reported to be involved in the regulation of the intestinal homeostasis through the regulation of endoplasmic reticulum (ER) stress in colonic epithelial cells. However, its role in CRC remains unclear. In this study, we found that colorectal tumours from human patients had decreased levels of RNF186. We demonstrated that overexpression of RNF186 suppressed the growth and migration of CRC-derived cell lines in vitro and inhibited tumour proliferation in vivo. Further, our findings indicated that forced expression of RNF186 inhibited nuclear factor-kappa B (NF-kappa B) activation by reducing the phosphorylation of NF-kappa B. In addition, our results showed that RNF186(-/-) mice exhibited significantly increased tumour burden compared to the wild type (WT) mice following treatment with azoxymethane/dextran sulfate sodium (AOM/DSS). Compared to WT mice, the percentage of Ki67 positive cells was increased in the RNF186(-/-) mice, indicating that RNF186 is crucial for intestinal cell proliferation during tumorigenesis. Taken together, our data suggest that RNF186 inhibits the development of CRC, and that this effect is mediated through the suppression of NF-kappa B activity.
机译：结肠直肠癌（CRC）是全球最常见的恶性胃肠癌之一。环形手指蛋白质186（RNF186）是无名指蛋白质家族的成员。据报道，RNF186通过调节结肠上皮细胞中的内质网（ER）胁迫来涉及肠道稳态的调节。然而，它在CRC中的作用仍然不清楚。在这项研究中，我们发现人类患者的结肠直肠肿瘤有降低的RNF186水平。我们证明，RNF186的过度表达抑制了体外CRC衍生细胞系的生长和迁移并抑制体内肿瘤增殖。此外，我们的研究结果表明RNF186的强迫表达通过减少NF-κB的磷酸化而抑制核因子-Kappa B（NF-Kappa B）活化。此外，我们的结果表明RNF186（ - / - ）小鼠表现出显着增加与氮氧基甲烷/葡聚糖硫酸钠（AOM / DSS）处理后，与野生型（WT）小鼠相比的肿瘤负担。与WT小鼠相比，RNF186（ - / - ）小鼠中ki67阳性细胞的百分比增加，表明RNF186对肿瘤发生期间的肠细胞增殖至关重要。我们的数据表明RNF186抑制CRC的发展，并且通过抑制NF-Kappa B活性来介导这种效果。

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  • 来源
    《Cellular Signalling》 |2020年第1期|共9页
  • 作者

    Ji Yizhong; Tu Xucan; Hu Xiuqi; Wang Zhenglin; Gao Sifan; Zhang Qifan; Zhang Wei; Zhang Huabing; Chen Wei;

  • 作者单位

    Anhui Med Univ Affiliated Hosp 1 Dept Gen Surg Hefei 230022 Anhui Peoples R China;

    Anhui Med Univ Affiliated Hosp 1 Dept Gen Surg Hefei 230022 Anhui Peoples R China;

    Anhui Med Univ Sch Basic Med Dept Biochem &

    Mol Biol Hefei 230032 Peoples R China;

    Anhui Med Univ Affiliated Hosp 1 Dept Gen Surg Hefei 230022 Anhui Peoples R China;

    Anhui Med Univ Affiliated Hosp 1 Dept Otorhinolaryngol Head &

    Neck Surg Hefei 230032 Peoples R China;

    Anhui Med Univ Sch Basic Med Dept Biochem &

    Mol Biol Hefei 230032 Peoples R China;

    Anhui Med Univ Clin Med Coll 2 Hefei 230032 Peoples R China;

    Anhui Med Univ Sch Basic Med Dept Biochem &

    Mol Biol Hefei 230032 Peoples R China;

    Anhui Med Univ Affiliated Hosp 1 Dept Gen Surg Hefei 230022 Anhui Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    RNF186; Colorectal cancer; NF-kappa B; Inflammation; Colitis-associated cancer;

    机译：RNF186;结肠直肠癌;NF-Kappa B;炎症;结肠炎相关癌症;

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