The long non-coding RNA MIAT/miR-139-5p/MMP2 axis regulates cell migration and invasion in non-small-cell lung cancer.

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.

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