MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer
| العنوان: | MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer |
|---|---|
| المؤلفون: | Ferri, C, Di Biase, A, Bocchetti, M, Zappavigna, S, Wagner, S, Le Vu, P, Luce, A, Cossu, AM, Vadakekolathu, J, Miles, A, Boocock, DJ, Robinson, A, Schwerdtfeger, M, Tirino, V, Papaccio, F, Caraglia, M, Regad, T, Desiderio, V |
| المساهمون: | 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., Desiderio, V. |
| المصدر: | Journal of Experimental & Clinical Cancer Research : CR JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA Consejo Superior de Investigaciones Científicas (CSIC) Journal of Experimental & Clinical Cancer Research, Vol 41, Iss 1, Pp 1-16 (2022) |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Cancer Research, Molecular biology, lncRNAs, Mice, Nude, Transfection, miR-423-5p, Mice, Malat-1, lncRNA, Animals, Humans, Cellular biology, Neoplasm Metastasis, RC254-282, miRNA, Cell Proliferation, Cancer, Research, Prostate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prostatic Neoplasms, Gene expression, miRNAs, MicroRNAs, Oncology |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1756-9966 0392-9078 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3cae88ad0b5a2e0bad42ba23b925360 https://irep.ntu.ac.uk/id/eprint/45385/1/1509639_Boocock.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c3cae88ad0b5a2e0bad42ba23b925360 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17569966 03929078 |
|---|