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

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Abstract

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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Acknowledgements

This work was supported by State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia (No.SKL-HIDCA-2017-Y8).

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  1. These author contributed equally.

Authors and Affiliations

  1. Department of Second Oncology, Xinjiang Traditional Chinese Medicine Hospital, Xinjiang, China

    Fanye Zeng

  2. Department of First Thoracic Surgery, Xinjiang Chest Hospital, Xinjiang, China

    Ning Yu

  3. Department of Otolaryngology Head and Neck Surgery, Xinjiang Urumqi Eye and ENT Hospital, Xinjiang, China

    Yanyan Han

  4. Department of Thoracic Surgery, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

    Julaiti Ainiwaer

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  1. Fanye Zeng
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  2. Ning Yu
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Correspondence to Julaiti Ainiwaer.

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All patients read and signed the informed consent forms and this experiment was approved by the First Affiliated Hospital of Xinjiang Medical University research ethics committee.

The animal experiments were approved by the Animal Experimental Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University.

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Communicated by Rita Mulherkar.

Corresponding editor: Rita Mulherkar

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Zeng, F., Yu, N., Han, Y. et al. The long non-coding RNA MIAT/miR-139-5p/MMP2 axis regulates cell migration and invasion in non-small-cell lung cancer. J Biosci 45, 51 (2020). https://doi.org/10.1007/s12038-020-0019-8

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