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

• Published in: Journal of biosciences 2020-12, Vol.45 (1), Article 51
• Main Authors: Zeng, Fanye, Yu, Ning, Han, Yanyan, Ainiwaer, Julaiti
• Format: Article
• Language: English
• Subjects: Animals; Assaying; Biomedical and Life Sciences; Biomedicine; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell adhesion & migration; Cell Biology; Cell Line, Tumor; Cell lines; Cell migration; Cell Movement - genetics; Cells; Cells, Cultured; Clonal deletion; DNA; Female; Gelatinase A; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Life Sciences; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lungs; Matrix Metalloproteinase 2 - metabolism; Metastases; Mice; Mice, Inbred BALB C; Mice, Nude; Microbiology; MicroRNAs - metabolism; Neoplasm Invasiveness; Neoplasms; Non-coding RNA; Non-small cell lung carcinoma; Nucleic acids; Nucleotide sequence; PCR; Plant Sciences; Restoration; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Long Noncoding - physiology; RNA-directed DNA polymerase; Small cell lung carcinoma; Tumor suppressor genes; Tumors; Western blotting; Zoology
• ISSN: 0250-5991; 0973-7138
• DOI: 10.1007/s12038-020-0019-8

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.