Non-small-cell lung cancer (NSCLC) is a complex disease which is influenced by multiple factors. Recent studies demonstrated that long non-coding RNA (lncRNA) MIAT was involved in tumor metastasis. However, the underlying mechanism of MIAT in NSCLC remains largely unknown. In this study, MIAT, miR-139-5p and MMP2 expression were measured by quantitative reverse transcriptase PCR (QRT-PCR) or Western blotting, respectively, and we found the expression of MIAT and MMP2 were elevated, while miR-139-5p was decreased in NSCLC tissues and cell lines. Transwell assay showed MIAT and MMP2 functioned as an oncogene to induce cell migration and invasion in NSCLC, but miR-139-5p served as a tumor suppressor in NSCLC to inhibit cell migration and invasion. Besides that, in vivo experiments also indicated MIAT deletion inhibited tumor growth. The relationship between miR-139-5p and MIAT or MMP2 was then confirmed by Luciferase reporter assay, and the results showed that MIAT directly interacted with miR-139-5p and miR-139-5p targetedly suppressed MMP2 in NSCLC cells. Furthermore, expression analysis showed that MIAT indirectly regulated MMP2 by sponging miR-139-5p. Finally, rescue assay suggested that miR-139-5p restoration reversed MIAT-overexpression-induced promotion on the migration and invasion of NSCLC cells. In conclusion, our results demonstrated that lncRNA MIAT modulated the migration and invasion of NSCLC by regulating miR-139-5p and MMP2.

中文翻译：

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长链非编码 RNA MIAT/miR-139-5p/MMP2 轴调控非小细胞肺癌细胞迁移和侵袭

非小细胞肺癌（NSCLC）是一种受多种因素影响的复杂疾病。最近的研究表明，长链非编码 RNA (lncRNA) MIAT 参与了肿瘤转移。然而，非小细胞肺癌中 MIAT 的潜在机制在很大程度上仍然未知。本研究分别通过定量逆转录酶聚合酶链反应（QRT-PCR）或蛋白质印迹法检测 MIAT、miR-139-5p 和 MMP2 的表达，发现 MIAT 和 MMP2 的表达升高，而 miR-139-5p在 NSCLC 组织和细胞系中减少。Transwell 检测显示 MIAT 和 MMP2 作为致癌基因在 NSCLC 中诱导细胞迁移和侵袭，而 miR-139-5p 在 NSCLC 中作为抑癌基因抑制细胞迁移和侵袭。除此之外，体内实验还表明 MIAT 缺失抑制了肿瘤生长。miR-139-5p 与 MIAT 或 MMP2 之间的关系随后通过荧光素酶报告基因检测证实，结果表明 MIAT 直接与 miR-139-5p 相互作用，miR-139-5p 靶向抑制 NSCLC 细胞中的 MMP2。此外，表达分析表明 MIAT 通过海绵 miR-139-5p 间接调节 MMP2。最后，救援试验表明 miR-139-5p 恢复逆转了 MIAT 过表达诱导的 NSCLC 细胞迁移和侵袭的促进作用。总之，我们的结果表明lncRNA MIAT通过调节miR-139-5p和MMP2来调节NSCLC的迁移和侵袭。表达分析表明 MIAT 通过海绵 miR-139-5p 间接调节 MMP2。最后，救援试验表明 miR-139-5p 恢复逆转了 MIAT 过表达诱导的 NSCLC 细胞迁移和侵袭的促进作用。总之，我们的结果表明lncRNA MIAT通过调节miR-139-5p和MMP2来调节NSCLC的迁移和侵袭。表达分析表明 MIAT 通过海绵 miR-139-5p 间接调节 MMP2。最后，救援试验表明 miR-139-5p 恢复逆转了 MIAT 过表达诱导的 NSCLC 细胞迁移和侵袭的促进作用。总之，我们的结果表明lncRNA MIAT通过调节miR-139-5p和MMP2来调节NSCLC的迁移和侵袭。