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抑癌 miR-128-3p 通过靶向 ZEB1 抑制食管鳞癌的转移和上皮间质转化。

Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting ZEB1 in esophageal squamous-cell cancer.

机构信息

Intensive Care Unit, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Chengdu 610000, China.

Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):171-180. doi: 10.1093/abbs/gmx132.

Abstract

MicroRNAs (miRNAs) are some short RNAs that regulate multiple biological functions at post-transcriptional levels, such as tumorigenic processes, inflammatory lesions and cell apoptosis. Zinc finger E-box binding homeobox factor 1 (ZEB1) is a crucial mediator of epithelial-mesenchymal transition (EMT). It induces malignant progression of various cancers including human esophageal squamous-cell carcinoma (ESCC). In this study, we found that miR-128-3p was downregulated in ESCC tissues and cells by using PCR. Moreover, down-regulated expression of miR-128-3p was testified to be associated with poor prognosis of ESCC patients and might be regarded as an independent prognostic factor. Then, we examined the role of miR-128-3p in ESCC cells, and found that miR-128-3p could suppress the cell migration and invasion in vitro. Furthermore, ZEB1 was confirmed to be a direct target of miR-128-3p by luciferase reporter assay. Rescue experiments proved that EMT was regulated by miR-128-3p via suppression of ZEB1. Taken all together, we conclude that miR-128-3p suppresses EMT and metastasis via ZEB1, and miR-128-3p may be a critical mediator in ESCC.

摘要

微小 RNA(miRNAs)是一些短 RNA,可在转录后水平调节多种生物学功能,如肿瘤发生过程、炎症损伤和细胞凋亡。锌指 E 盒结合同源盒因子 1(ZEB1)是上皮-间充质转化(EMT)的关键介质。它诱导包括人食管鳞状细胞癌(ESCC)在内的各种癌症的恶性进展。在本研究中,我们使用 PCR 发现 miR-128-3p 在 ESCC 组织和细胞中下调。此外,miR-128-3p 的下调表达被证明与 ESCC 患者的不良预后相关,并且可能被视为独立的预后因素。然后,我们研究了 miR-128-3p 在 ESCC 细胞中的作用,发现 miR-128-3p 可以抑制体外细胞迁移和侵袭。此外,通过荧光素酶报告基因检测证实 ZEB1 是 miR-128-3p 的直接靶标。挽救实验证明 EMT 通过抑制 ZEB1 被 miR-128-3p 调控。综上所述,我们得出结论,miR-128-3p 通过抑制 ZEB1 抑制 EMT 和转移,miR-128-3p 可能是 ESCC 中的关键介质。

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