MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer
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 mechan...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-02233-w |
| _version_ | 1818752829130539008 |
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| author | Carmela Ferri Anna Di Biase Marco Bocchetti Silvia Zappavigna Sarah Wagner Pauline Le Vu Amalia Luce Alessia Maria Cossu Jayakumar Vadakekolathu Amanda Miles David J. Boocock Alex Robinson Melanie Schwerdtfeger Virginia Tirino Federica Papaccio Michele Caraglia Tarik Regad Vincenzo Desiderio |
| author_facet | Carmela Ferri Anna Di Biase Marco Bocchetti Silvia Zappavigna Sarah Wagner Pauline Le Vu Amalia Luce Alessia Maria Cossu Jayakumar Vadakekolathu Amanda Miles David J. Boocock Alex Robinson Melanie Schwerdtfeger Virginia Tirino Federica Papaccio Michele Caraglia Tarik Regad Vincenzo Desiderio |
| author_sort | Carmela Ferri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T04:57:41Z |
| format | Article |
| id | doaj.art-6775aa52ba8e4162a369ebbfb370a0a7 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-18T04:57:41Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-6775aa52ba8e4162a369ebbfb370a0a72022-12-21T21:20:14ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-01-0141111610.1186/s13046-021-02233-wMiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancerCarmela Ferri0Anna Di Biase1Marco Bocchetti2Silvia Zappavigna3Sarah Wagner4Pauline Le Vu5Amalia Luce6Alessia Maria Cossu7Jayakumar Vadakekolathu8Amanda Miles9David J. Boocock10Alex Robinson11Melanie Schwerdtfeger12Virginia Tirino13Federica Papaccio14Michele Caraglia15Tarik Regad16Vincenzo Desiderio17Department of Precision Medicine, University of Campania “Luigi Vanvitelli”The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent UniversityDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent UniversityClinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of SouthamptonDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic ResearchThe John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent UniversityThe John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent UniversityThe John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent UniversityDepartment of Life Sciences, Faculty of Health, Education and Life Sciences, Birmingham City UniversityDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of SalernoDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”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.https://doi.org/10.1186/s13046-021-02233-wProstateCancermiRNAslncRNAsmiR-423-5pMalat-1 |
| spellingShingle | Carmela Ferri Anna Di Biase Marco Bocchetti Silvia Zappavigna Sarah Wagner Pauline Le Vu Amalia Luce Alessia Maria Cossu Jayakumar Vadakekolathu Amanda Miles David J. Boocock Alex Robinson Melanie Schwerdtfeger Virginia Tirino Federica Papaccio Michele Caraglia Tarik Regad Vincenzo Desiderio MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer Journal of Experimental & Clinical Cancer Research Prostate Cancer miRNAs lncRNAs miR-423-5p Malat-1 |
| title | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
| title_full | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
| title_fullStr | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
| title_full_unstemmed | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
| title_short | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
| title_sort | mir 423 5p prevents malat1 mediated proliferation and metastasis in prostate cancer |
| topic | Prostate Cancer miRNAs lncRNAs miR-423-5p Malat-1 |
| url | https://doi.org/10.1186/s13046-021-02233-w |
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