Department of Surgery 1, Guilin Tcm Hospital of China, Guilin City, Guangxi Zhuang Autonomous Region, China.
Department of General Surgery, Nantong Tumor Hospital, Nantong City, Jiangsu Province, China.
Bioengineered. 2021 Dec;12(2):12060-12069. doi: 10.1080/21655979.2021.2003664.
Colorectal cancer (CRC) is ranked as the third most common malignancy worldwide. Therefore, it is urgent to screen novel and effective molecular drug targets for colorectal cancer therapeutics. In this study, the specific role and related mechanism underlying Ring finger (RNF) 220 in colon cancer were investigated. Firstly, RT-PCR assay was used to compare differences between expression levels of RNF220 in colorectal tumor and normal tissues. Western blot and RT-PCR assays were applied to examine the protein levels of RNF220 in normal colonic mucosa and colorectal cancer cells. We found that RNF220 was upregulated in colorectal cancer in patients and cell models. RNF220 promoted the proliferation and migration, invasion of colorectal cancer cells through BrdU incorporation, clone formation, transwell and wound healing assays. Spheroid formation and western blot assays illustrated that RNF220 promoted the stemness of colorectal cancer cells. Moreover, we found that RNF220 regulated BMI1 expression through USP22 by western blot. Finally, we discovered that RNF220 facilitated tumor growth through establishment of subcutaneous xenograft tumor mice model. In conclusion, RNF220 promoted the stemness and progression of colon cancer cells via the USP22-BMI1 axis.
结直肠癌（CRC）是全球排名第三的常见恶性肿瘤。因此，迫切需要筛选新型有效的结直肠癌治疗分子药物靶点。本研究旨在探讨环指（RNF）220 在结肠癌中的特定作用及相关机制。首先，通过 RT-PCR 检测比较结直肠肿瘤组织和正常组织中 RNF220 的表达差异。通过 Western blot 和 RT-PCR 检测，检测正常结肠黏膜和结直肠癌细胞中 RNF220 的蛋白水平。结果显示，RNF220 在患者和细胞模型中的结直肠癌中上调。通过 BrdU 掺入、克隆形成、Transwell 和划痕愈合实验，RNF220 促进了结直肠癌细胞的增殖和迁移、侵袭。球体形成和 Western blot 实验表明，RNF220 通过 USP22 促进了结直肠癌细胞的干性。此外，我们通过 Western blot 发现 RNF220 通过 USP22 调节 BMI1 的表达。最后，我们通过建立皮下异种移植瘤小鼠模型发现 RNF220 促进肿瘤生长。综上所述，RNF220 通过 USP22-BMI1 轴促进结肠癌细胞的干性和进展。
