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Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer
BACKGROUND: Prostate cancer remains one of the deadliest neoplasms in developed countries. Identification of new molecular markers that predict the onset and progression of the disease could improve its clinical management. Low miR-145-5p expression is consistently found in primary tumors and metast...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334624/ https://www.ncbi.nlm.nih.gov/pubmed/37434219 http://dx.doi.org/10.1186/s13062-023-00393-7 |
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author | Le Hars, Matthieu Castro-Vega, Luis Jaime Rajabi, Fatemeh Tabatadze, David Romero, Martha Pinskaya, Marina Groisman, Irina |
author_facet | Le Hars, Matthieu Castro-Vega, Luis Jaime Rajabi, Fatemeh Tabatadze, David Romero, Martha Pinskaya, Marina Groisman, Irina |
author_sort | Le Hars, Matthieu |
collection | PubMed |
description | BACKGROUND: Prostate cancer remains one of the deadliest neoplasms in developed countries. Identification of new molecular markers that predict the onset and progression of the disease could improve its clinical management. Low miR-145-5p expression is consistently found in primary tumors and metastases, but the regulatory mechanisms governing its functions remain largely unknown. METHODS: Bioinformatics analysis was conducted to identify [1] a set of novel potential competing endogenous lncRNAs for sponging of miRNA-145-5p in prostate cancer and [2] miR-145-5p and other EMT-related miRNAs response elements in lnc-ZNF30-3. Quantification of miR-145-5p, lnc-ZNF30-3, and TWIST1 expression levels in tumor tissues in RNA sequencing datasets of our and TCGA PRAD cohorts revealed a correlation with clinical outcome of prostate cancer patients. Biochemical and cell biology approaches, such as RNA pull-down, western blot, immunostaining, and wound healing assays were used for evaluation of the impact of TWIST1/miR-145/ lnc-ZNF30-3 interactions in prostate cancer cells altered in miRNA and lncRNA expression. RESULTS: We identified a few potential lncRNA sponges of miR-145-5p, including lnc-ZNF30-3. It contains five response elements for miR-145-5p, but also other miRNAs targeting EMT transcription factors. Lnc-ZNF30-3 is significantly upregulated in prostate cancer cell lines and tumor tissues, and its high expression is correlated with poor patient prognosis. We demonstrated that lnc-ZNF30-3 is associated with AGO2 and specifically interacts with the miR-145-5p seed region. Knockdown of lnc-ZNF30-3 results in decreased migration of prostate cancer cells and downregulation of EMT drivers such as TWIST1 and ZEB1 at both the RNA and protein levels. These phenotypic and molecular features of lnc-ZNF30-3-depleted cells are partially rescued by miR-145-5p inhibition. CONCLUSIONS: Collectively, our results point to lnc-ZNF30-3 as a novel competing endogenous lncRNA for miR-145-5p and other miRNAs that target TWIST1 as well as other EMT transcription factors. Prostate cancer patients with high lncRNA expression in primary tumors show lower survival rate suggesting that lnc-ZNF30-3 may contribute to prostate cancer progression and metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00393-7. |
format | Online Article Text |
id | pubmed-10334624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103346242023-07-12 Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer Le Hars, Matthieu Castro-Vega, Luis Jaime Rajabi, Fatemeh Tabatadze, David Romero, Martha Pinskaya, Marina Groisman, Irina Biol Direct Comment BACKGROUND: Prostate cancer remains one of the deadliest neoplasms in developed countries. Identification of new molecular markers that predict the onset and progression of the disease could improve its clinical management. Low miR-145-5p expression is consistently found in primary tumors and metastases, but the regulatory mechanisms governing its functions remain largely unknown. METHODS: Bioinformatics analysis was conducted to identify [1] a set of novel potential competing endogenous lncRNAs for sponging of miRNA-145-5p in prostate cancer and [2] miR-145-5p and other EMT-related miRNAs response elements in lnc-ZNF30-3. Quantification of miR-145-5p, lnc-ZNF30-3, and TWIST1 expression levels in tumor tissues in RNA sequencing datasets of our and TCGA PRAD cohorts revealed a correlation with clinical outcome of prostate cancer patients. Biochemical and cell biology approaches, such as RNA pull-down, western blot, immunostaining, and wound healing assays were used for evaluation of the impact of TWIST1/miR-145/ lnc-ZNF30-3 interactions in prostate cancer cells altered in miRNA and lncRNA expression. RESULTS: We identified a few potential lncRNA sponges of miR-145-5p, including lnc-ZNF30-3. It contains five response elements for miR-145-5p, but also other miRNAs targeting EMT transcription factors. Lnc-ZNF30-3 is significantly upregulated in prostate cancer cell lines and tumor tissues, and its high expression is correlated with poor patient prognosis. We demonstrated that lnc-ZNF30-3 is associated with AGO2 and specifically interacts with the miR-145-5p seed region. Knockdown of lnc-ZNF30-3 results in decreased migration of prostate cancer cells and downregulation of EMT drivers such as TWIST1 and ZEB1 at both the RNA and protein levels. These phenotypic and molecular features of lnc-ZNF30-3-depleted cells are partially rescued by miR-145-5p inhibition. CONCLUSIONS: Collectively, our results point to lnc-ZNF30-3 as a novel competing endogenous lncRNA for miR-145-5p and other miRNAs that target TWIST1 as well as other EMT transcription factors. Prostate cancer patients with high lncRNA expression in primary tumors show lower survival rate suggesting that lnc-ZNF30-3 may contribute to prostate cancer progression and metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00393-7. BioMed Central 2023-07-11 /pmc/articles/PMC10334624/ /pubmed/37434219 http://dx.doi.org/10.1186/s13062-023-00393-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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. |
spellingShingle | Comment Le Hars, Matthieu Castro-Vega, Luis Jaime Rajabi, Fatemeh Tabatadze, David Romero, Martha Pinskaya, Marina Groisman, Irina Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title | Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title_full | Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title_fullStr | Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title_full_unstemmed | Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title_short | Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer |
title_sort | pro-tumorigenic role of lnc-znf30-3 as a sponge counteracting mir-145-5p in prostate cancer |
topic | Comment |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334624/ https://www.ncbi.nlm.nih.gov/pubmed/37434219 http://dx.doi.org/10.1186/s13062-023-00393-7 |
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