miR-25 通过抑制 KLF4 增强非小细胞肺癌细胞中的 ERK 信号通路，从而促进细胞迁移和侵袭。
miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells via ERK signaling pathway by inhibiting KLF4.
机构信息
Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Graduate Student Major of Laboratory Medicine of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
出版信息
Mol Med Rep. 2018 May;17(5):7005-7016. doi: 10.3892/mmr.2018.8772. Epub 2018 Mar 16.
In recent years, microRNAs (miRNAs/miRs) have gained increasing interest in cancer research. Increasing evidences demonstrated that miRNAs are important for tumor early detection and prognosis. The present study aimed to explore the function of miR‑25 in non‑small‑cell lung cancer (NSCLC) and its underlying mechanisms. The expression levels of miR‑25 and Krüppel-like factor 4 (KLF4) were assessed in 31 pairs of tissue from patients with NSCLC. In addition, the biological roles of miR‑25 in NSCLC were analyzed via a cell wound healing assay, Transwell invasion and migration assays. Target genes of miR‑25 were predicted using TargetScan and verified via a dual luciferase activity assay, western blotting and reverse transcription‑quantitative polymerase chain reaction. The downstream signaling pathway was confirmed by western blot analysis. In the present study, miR‑25 was overexpressed in 31 NSCLC samples compared with in corresponding normal tissues. Overexpression of miR‑25 using miR‑25 mimics markedly promoted NSCLC cell migration and invasion, while inhibition of miR‑25 exerted the opposite effect. KLF4 was suggested to be a novel target gene of miR‑25 in NSCLC cells. Knockdown of KLF4 promoted the migration and invasion of NSCLC cells, whereas rescue of KLF4 expression reduced cell motion ability in miR‑25‑overexpressing NSCLC cells. Furthermore, it was demonstrated that miR‑25 activated the extracellular signal‑regulated kinase (ERK) signaling pathway, which eventually led to increased vimentin, matrix metalloproteinase 11 and N‑cadherin levels, and the downregulation of E‑cadherin expression by inhibiting the expression of KLF4. In conclusion, miR‑25 was demonstrated to activate the ERK signaling pathway by directly targeting KLF4, promoting cell migration and invasion. The findings of the present study indicated that miR‑25 or KLF4 may serve as a therapeutic target for the treatment of NSCLC.
近年来，微小 RNA（miRNAs/miRs）在癌症研究中受到越来越多的关注。越来越多的证据表明，miRNAs 对肿瘤的早期检测和预后具有重要意义。本研究旨在探讨 miR-25 在非小细胞肺癌（NSCLC）中的功能及其潜在机制。评估了 31 对 NSCLC 患者组织中 miR-25 和 Krüppel 样因子 4（KLF4）的表达水平。此外，通过细胞划痕愈合试验、Transwell 侵袭和迁移试验分析了 miR-25 在 NSCLC 中的生物学作用。使用 TargetScan 预测 miR-25 的靶基因，并通过双荧光素酶活性测定、Western blot 和逆转录-定量聚合酶链反应进行验证。通过 Western blot 分析确认下游信号通路。在本研究中，与相应的正常组织相比，31 例 NSCLC 样本中 miR-25 表达上调。用 miR-25 模拟物过表达 miR-25 显著促进 NSCLC 细胞迁移和侵袭，而抑制 miR-25 则产生相反的效果。KLF4 被认为是 NSCLC 细胞中 miR-25 的一个新的靶基因。敲低 KLF4 促进 NSCLC 细胞的迁移和侵袭，而恢复 KLF4 的表达则降低了 miR-25 过表达 NSCLC 细胞的细胞运动能力。此外，研究表明 miR-25 通过直接靶向 KLF4 激活细胞外信号调节激酶（ERK）信号通路，最终导致波形蛋白、基质金属蛋白酶 11 和 N-钙粘蛋白水平升高，E-钙粘蛋白表达下调。综上所述，miR-25 通过直接靶向 KLF4 激活 ERK 信号通路，促进细胞迁移和侵袭。本研究的结果表明，miR-25 或 KLF4 可能作为 NSCLC 治疗的潜在靶点。
Zotero 插件