Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
Mol Med Rep. 2017 Dec;16(6):9067-9073. doi: 10.3892/mmr.2017.7758. Epub 2017 Oct 10.
Gastric cancer is the fourth most common malignancy and the third leading cause of cancer‑associated mortality globally. Accumulating studies have identified the involvement of microRNAs in the initiation and progression of gastric cancer. This study was aimed to investigate the expression, functional roles of microRNA‑454 (miR‑454) and its direct target gene in gastric cancer. According to the results, the expression level of miR‑454 was demonstrated to be reduced in gastric cancer tissues and cell lines compared with corresponding distant non‑tumor gastric tissues and human immortalized gastric epithelial, respectively. miR‑454 mimic transfection led to inhibition of gastric cancer cells proliferation, migration and invasion in vitro. Bioinformatic analysis predicated that zinc finger E‑box‑binding homeobox 1 (ZEB1) is a potential target gene of miR‑454. Luciferase reporter assays revealed that miR‑454 directly targeted the 3'UTR of ZEB1. miR‑454 overexpression significantly decreased the ZEB1 mRNA and protein expression levels. ZEB1 knockdown could mimic the tumor suppressive roles induced by miR‑454 overexpression on gastric cancer cell proliferation, migration and invasion. In conclusion, the present study suggested that miR‑454 under expression may be involved in gastric cancer initiation and progression, by promoting proliferation, migration and invasion by directly targeting ZEB1. miR‑454/ZEB1‑based targeted therapy may be a potential strategy for the treatment of gastric cancer.
胃癌是第四大常见恶性肿瘤，也是全球癌症相关死亡的第三大主要原因。越来越多的研究已经确定了 microRNAs 在胃癌的发生和发展中的作用。本研究旨在探讨 microRNA-454（miR-454）及其直接靶基因在胃癌中的表达和功能作用。根据研究结果，与相应的远端非肿瘤性胃组织和人永生化胃上皮细胞相比，胃癌组织和细胞系中 miR-454 的表达水平降低。miR-454 模拟物转染导致体外胃癌细胞增殖、迁移和侵袭受到抑制。生物信息学分析预测锌指 E-框结合同源盒 1（ZEB1）是 miR-454 的潜在靶基因。荧光素酶报告基因检测显示，miR-454 可直接靶向 ZEB1 的 3'UTR。miR-454 过表达显著降低了 ZEB1 mRNA 和蛋白表达水平。ZEB1 敲低可模拟 miR-454 过表达对胃癌细胞增殖、迁移和侵袭的肿瘤抑制作用。总之，本研究表明 miR-454 表达下调可能参与胃癌的发生和发展，通过直接靶向 ZEB1 促进增殖、迁移和侵袭。基于 miR-454/ZEB1 的靶向治疗可能是治疗胃癌的一种潜在策略。
