Ji Yizhong, Tu Xucan, Hu Xiuqi, Wang Zhenglin, Gao Sifan, Zhang Qifan, Zhang Wei, Zhang Huabing, Chen Wei
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
Cell Signal. 2020 Nov;75:109764. doi: 10.1016/j.cellsig.2020.109764. Epub 2020 Sep 1.
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-κB (NF-κB) activation by reducing the phosphorylation of NF-κB. 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-κB activity.
结直肠癌（CRC）是全球最常见的恶性胃肠道癌症之一。环指蛋白186（RNF186）是环指蛋白家族的成员。据报道，RNF186通过调节结肠上皮细胞内质网（ER）应激参与肠道稳态的调节。然而，其在结直肠癌中的作用仍不清楚。在本研究中，我们发现人类患者的结直肠肿瘤中RNF186水平降低。我们证明，RNF186的过表达在体外抑制了结直肠癌衍生细胞系的生长和迁移，并在体内抑制了肿瘤增殖。此外，我们的研究结果表明，RNF186的强制表达通过减少核因子-κB（NF-κB）的磷酸化来抑制NF-κB的激活。另外，我们的结果显示，在用氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）处理后，RNF186小鼠的肿瘤负担比野生型（WT）小鼠显著增加。与WT小鼠相比，RNF186小鼠中Ki67阳性细胞的百分比增加，表明RNF186在肿瘤发生过程中对肠道细胞增殖至关重要。综上所述，我们的数据表明RNF186抑制结直肠癌的发展，并且这种作用是通过抑制NF-κB活性介导的。
