Xue Liang, Yang Dong
Department of Gastrointestinal Surgery and 2Department of Anorectal Surgery, the First People's Hospital of Lianyungang (Affiliated Hospital of Kangda College of Nanjing Medical University), Lianyungang, China.
J BUON. 2018 Nov-Dec;23(6):1633-1639.
To investigate the role and molecular mechanism of miR-421 in the development of colorectal cancer (CRC), providing a theoretical basis for the search for new CRC therapeutic targets.
30 pairs of human CRC and cancer-adjacent normal tissue samples were collected. The expression of miR-421 was detected in CRC tissues and cells. On-line target gene prediction software was applied to screen metastasis-associated protein 1 (MTA1), the potential downstream target gene of miR-421. The role of miR-421 in regulating MTA1 and its effect on the expression of epithelial-mesenchymal transition (EMT) markers (E-cadherinand Vimentin) were detected.
Compared with that in adjacent normal tissues and normal human intestinal epithelial cells, the miR-421expression level in CRC tissues and cells was significantly reduced. The potential target of miR-421 was analyzed by three public databases, in which we found that MTA1 was a direct target of miR-421, and miR-421 inhibited the proliferation, invasion, migration and EMT of CRC cells through the targeted regulation of the expression of target gene MTA1, thus effectively suppressing the ability of CRC cells.
This research demonstrated the suppressive function of miR-421 in CRC. Therefore, the miR-421/MAT1 axis is expected to be one of the targets of CRC targeted therapy.
探讨miR - 421在结直肠癌（CRC）发生发展中的作用及分子机制，为寻找新的CRC治疗靶点提供理论依据。
收集30对人CRC组织及癌旁正常组织样本。检测CRC组织和细胞中miR - 421的表达。应用在线靶基因预测软件筛选miR - 421潜在的下游靶基因转移相关蛋白1（MTA1）。检测miR - 421对MTA1的调控作用及其对上皮间质转化（EMT）标志物（E - cadherin和波形蛋白）表达的影响。
与癌旁正常组织和正常人肠上皮细胞相比，CRC组织和细胞中miR - 421表达水平显著降低。通过三个公共数据库分析miR - 421的潜在靶点，发现MTA1是miR - 421的直接靶点，miR - 421通过靶向调控靶基因MTA1的表达抑制CRC细胞的增殖、侵袭、迁移及EMT，从而有效抑制CRC细胞的能力。
本研究证实了miR - 421在CRC中的抑制作用。因此，miR - 421/MAT1轴有望成为CRC靶向治疗的靶点之一。
