miR-126 通过调控 ZEB1 抑制宫颈癌的迁移和侵袭。
The inhibition of miR-126 in cell migration and invasion of cervical cancer through regulating ZEB1.
机构信息
1Department of Gynaecology and Obstetrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing Medical University, No. 321 Zhongshan Road, Gulou District, Nanjing, 210008 Jiangsu China.
2Department of Gynaecology and Obstetrics, Shuyang People's Hospital, Shuyang Hospital Affiliated to Xuzhou Medical University, Suqian, 223600 Jiangsu China.
出版信息
Hereditas. 2019 Apr 9;156:11. doi: 10.1186/s41065-019-0087-7. eCollection 2019.
BACKGROUND
Cervical 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.
RESULTS
Firstly, 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.
CONCLUSION
miR-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.
背景
宫颈癌是一种常见于女性的恶性肿瘤，具有全球范围内高发病率和死亡率的特点。微小 RNA（miRNA）在人类癌症的发展中起着关键作用。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，通过 RT-qPCR 检测发现，与正常相邻组织和正常宫颈上皮细胞系（Ect1/E6E7）相比，miR-126 在宫颈癌组织和细胞系中的表达明显下调。然后，通过荧光素酶报告基因检测验证 ZEB1 是 miR-126 的靶基因。相反，在肿瘤组织中 ZEB1 的表达显著上调，并且其 mRNA 水平在 SiHa 和 Hela 细胞中受 miR-126 表达的负调控。此外，通过 CCK-8 实验、划痕愈合实验和 Transwell 实验分别分析了细胞增殖、迁移和侵袭能力。结果表明，过表达 miR-126 抑制了 SiHa 和 Hela 细胞的增殖、迁移和侵袭，而 ZEB1 则消除了 miR-126 诱导的抑制作用。此外，miR-126 在 mRNA 和蛋白水平上抑制 MMP2 和 MMP9 的表达，并抑制了 SiHa 和 Hela 细胞中 JAK2/STAT3 信号通路的磷酸化，而 ZEB1 则挽救了 miR-126 诱导的抑制作用。
结论
miR-126 在体外作为宫颈癌细胞的肿瘤抑制因子发挥作用，通过抑制 MMP2、MMP9 的表达和使 JAK2/STAT3 信号通路失活，从而抑制细胞的增殖、迁移和侵袭，表明 miR-126 可能成为宫颈癌患者诊断和治疗的新靶点。
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