MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer

Ferri, C., Di Biase, A. ORCID: 0000-0002-4988-8798, Bocchetti, M., Zappavigna, S., Wagner, S. ORCID: 0000-0002-5221-9851, Le Vu, P., Luce, A., Cossu, A.M., Vadakekolathu, J. ORCID: 0000-0002-2671-4285, Miles, A. ORCID: 0000-0002-5388-938X, Boocock, D.J. ORCID: 0000-0002-7333-3549, Robinson, A. ORCID: 0000-0001-8247-424X, Schwerdtfeger, M., Tirino, V., Papaccio, F., Caraglia, M., Regad, T. ORCID: 0000-0003-4028-6368 and Desiderio, V., 2022. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. Journal of Experimental and Clinical Cancer Research, 41 (1): 40. ISSN 1756-9966

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Abstract

Background: The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs).

Methods: Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa.

Results: Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model.

Conclusions: We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.

Item Type: Journal article
Publication Title: Journal of Experimental and Clinical Cancer Research
Creators: Ferri, C., Di Biase, A., Bocchetti, M., Zappavigna, S., Wagner, S., Le Vu, P., Luce, A., Cossu, A.M., Vadakekolathu, J., Miles, A., Boocock, D.J., Robinson, A., Schwerdtfeger, M., Tirino, V., Papaccio, F., Caraglia, M., Regad, T. and Desiderio, V.
Publisher: Springer Science and Business Media LLC
Date: 2022
Volume: 41
Number: 1
ISSN: 1756-9966
Identifiers:
NumberType
10.1186/s13046-021-02233-wDOI
1509639Other
Rights: © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 24 Jan 2022 09:19
Last Modified: 24 Jan 2022 09:19
URI: http://irep.ntu.ac.uk/id/eprint/45385

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