Zhou Haibo, Yang Li, Xu Xinhua, Lu Mingqian, Guo Rong, Li Daojun, Huang Qiao, Liu Yang, Deng Glenn, Xu Yalin
Institute of Oncology, The First College of Clinical Medical Science, Yichang Central People's Hospital Affiliated to China Three Gorges University, Yichang, Hubei 443000, P.R. China.
Department of Thyroid and Breast, The First College of Clinical Medical Science, Yichang Central People's Hospital Affiliated to China Three Gorges University, Yichang, Hubei 443000, P.R. China.
Oncol Lett. 2019 Jan;17(1):706-712. doi: 10.3892/ol.2018.9593. Epub 2018 Oct 17.
Downregulation of microRNA-34a (miR-34a) has frequently been observed in esophageal squamous cell carcinoma (ESCC). However, the underlying role and molecular mechanism of miR-34a in ESCC remains largely unknown. In the current study, it was demonstrated that miR-34a was downregulated and forkhead box M1 (FOXM1), a target gene of miR-34a, was upregulated in ESCC tumor tissues. Overexpression of miR-34a decreased FOXM1 mRNA and protein expression in the ESCC cell lines tested (TE-1 and TE-8). Inhibition of miR-34a increased FOXM1 mRNA and protein levels in human esophageal epithelial cells (HEEC). In addition, miR-34a mimics reduced the relative luciferase activity of ESCC cells transfected with FOXM1 3'UTR-WT, but not FOXM1 3'UTR-Mut. The CCK8 assay and scratch wound healing assay showed that overexpression of miR-34a induced inhibition of cell proliferation and cell migration. Additionally, transfection with miR-34a mimics reduced the expression of key genes involved in cell migration (MMP2 and MMP9) in ESCC cells. Thus, the present data demonstrated that miR-34a suppressed ESCC progression by directly targeting FOXM1.
在食管鳞状细胞癌（ESCC）中，经常观察到微小RNA-34a（miR-34a）表达下调。然而，miR-34a在ESCC中的潜在作用和分子机制仍 largely未知。在本研究中，结果表明，在ESCC肿瘤组织中miR-34a表达下调，而miR-34a的靶基因叉头框M1（FOXM1）表达上调。miR-34a过表达降低了所检测的ESCC细胞系（TE-1和TE-8）中FOXM1的mRNA和蛋白表达。抑制miR-34a可提高人食管上皮细胞（HEEC）中FOXM1的mRNA和蛋白水平。此外，miR-34a模拟物降低了转染FOXM1 3'UTR-WT的ESCC细胞的相对荧光素酶活性，但对转染FOXM1 3'UTR-Mut的细胞无此作用。CCK8实验和划痕伤口愈合实验表明，miR-34a过表达可抑制细胞增殖和细胞迁移。此外，转染miR-34a模拟物可降低ESCC细胞中参与细胞迁移的关键基因（MMP2和MMP9）的表达。因此，本研究数据表明，miR-34a通过直接靶向FOXM1抑制ESCC进展。
