BackgroundCervical cancer is a malignancy that’s common in female with high incidence and mortality worldwide. MicroRNAs (miRNAs) act a pivotal part in human cancer development. Our aim was to investigate the effect of miR-126 on cervical cancer and its underlying molecular mechanism.ResultsFirstly, RT-qPCR assay revealed that the expression of miR-126 was significantly downregulated in cervical cancer tissues and cell lines, compared with that in normal adjacent tissues and normal cervical epithelial cell line (Ect1/E6E7), respectively. Then, ZEB1 was verified as a target of miR-126 by using luciferase reporter assay. Inversely, the expression of ZEB1 was markedly upregulated in tumor tissues, and its mRNA level was negatively regulated by miR-126 expression in SiHa and Hela cells. Moreover, the capability of cell proliferation, migration and invasion was analyzed by CCK-8, wound healing assay and transwell assay, respectively. The results demonstrated that overexpression of miR-126 inhibited SiHa and Hela cell proliferation, migration and invasion, while ZEB1 abolished the inhibition induced by miR-126. Additionally, miR-126 suppressed MMP2 and MMP9 in mRNA and protein levels, as well as inhibited the protein expression of p-JAK2 and p-STAT3 in both SiHa and Hela cells, while ZEB1 rescued miR-126-induced suppression.ConclusionmiR-126 functions as a tumor suppressor in cervical cancer cells in vitro, which inhibits the proliferation, migration and invasion by suppressing MMP2, MMP9 expression and inactivating JAK2/STAT3 signaling pathway through targeting ZEB1, suggesting that miR-126 might be a novel potential target for the diagnosis and treatment of patients with cervical cancer.

中文翻译：

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miR-126通过调控ZEB1抑制宫颈癌细胞迁移和侵袭

背景宫颈癌是一种常见于女性的恶性肿瘤，在全球范围内发病率和死亡率都很高。MicroRNAs (miRNAs) 在人类癌症发展中发挥着关键作用。我们的目的是研究miR-126对宫颈癌的影响及其潜在的分子机制。结果首先，RT-qPCR检测显示，与正常细胞相比，miR-126在宫颈癌组织和细胞系中的表达显着下调。邻近组织和正常宫颈上皮细胞系 (Ect1/E6E7)。然后，通过使用荧光素酶报告基因测定，验证 ZEB1 是 miR-126 的靶标。相反，ZEB1 在肿瘤组织中的表达显着上调，其 mRNA 水平受到 SiHa 和 Hela 细胞中 miR-126 表达的负调控。此外，细胞增殖能力，分别通过CCK-8、伤口愈合试验和transwell试验分析迁移和侵袭。结果表明，miR-126的过表达抑制了SiHa和Hela细胞的增殖、迁移和侵袭，而ZEB1消除了miR-126诱导的抑制作用。此外，在 SiHa 和 Hela 细胞中，miR-126 抑制 MMP2 和 MMP9 的 mRNA 和蛋白质水平，并抑制 p-JAK2 和 p-STAT3 的蛋白质表达，而 ZEB1 挽救了 miR-126 诱导的抑制。 结论 miR-126在体外作为宫颈癌细胞的肿瘤抑制因子，通过靶向 ZEB1 抑制 MMP2、MMP9 的表达和灭活 JAK2/STAT3 信号通路来抑制增殖、迁移和侵袭，