Department of Gastrointestinal Surgery, Cancer Hospital of 74790Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
B-Ultrasound Room, Cancer Hospital of 74790Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820967475. doi: 10.1177/1533033820967475.
Dysregulated microRNAs (miRNAs) have been implicated in the pathogenic processes of colon cancer. Epithelial mesenchymal transition (EMT) promotes metastatic progression and cancer stem cells are closely involved in colon cancer proliferation and metastasis. Functional effects of miR-377 on colon cancer stem cell phenotypes and EMT were then determined in the present study. Firstly, reduced miR-377 was found in colon cancer tissues and cell lines. Results from flow cytometry, sphere formation and western blot assays showed that miR-377 knockdown increased number of ALDH+ cells and promoted sphere formation ability. Moreover, cell migration/invasion and EMT of colon cancer cells were suppressed by miR-377 over-expression. On the contrary, miR-377 mimics caused the reversed results. ZEB2 (zinc finger E box-binding homeobox 2) was then validated as a binding target of miR-377. ZEB2 over-expression reversed the inhibitory abilities of miR-377 on cancer stem cell phenotypes, EMT, migration and invasion. In conclusion, miR-377 regulates cancer stem cell phenotypes and EMT in colon cancer cells via regulation of ZEB2, suggesting a new therapeutic strategy for colon cancer treatment.
失调的 microRNAs（miRNAs）已被牵连到结肠癌的发病过程中。上皮-间充质转化（EMT）促进转移进展，而癌症干细胞则密切参与结肠癌的增殖和转移。本研究旨在确定 miR-377 对结肠癌干细胞表型和 EMT 的功能影响。首先，在结肠癌组织和细胞系中发现 miR-377 减少。流式细胞术、球体形成和 Western blot 分析的结果表明，miR-377 敲低增加了 ALDH+细胞的数量，并促进了球体形成能力。此外，miR-377 的过表达抑制了结肠癌细胞的迁移/侵袭和 EMT。相反，miR-377 模拟物则导致相反的结果。锌指 E 盒结合同源盒 2（ZEB2）随后被验证为 miR-377 的结合靶标。ZEB2 的过表达逆转了 miR-377 对癌症干细胞表型、EMT、迁移和侵袭的抑制作用。总之，miR-377 通过调节 ZEB2 调节结肠癌细胞中的癌症干细胞表型和 EMT，为结肠癌的治疗提供了新的治疗策略。
