Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells
Tumor suppressor microRNAs (miRNAs) have been explored as agents to target cancer stem cells. Most strategies use a single miRNA mimic and present many disadvantages, such as the amount of reagent required and the diluted effect on target genes. miRNAs work in a cooperative fashion to regulate disti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/2/289 |
| _version_ | 1797411630326218752 |
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| author | Adam Kosti Rodrigo Barreiro Gabriela D. A. Guardia Shiva Ostadrahimi Erzsebet Kokovay Alexander Pertsemlidis Pedro A. F. Galante Luiz O. F. Penalva |
| author_facet | Adam Kosti Rodrigo Barreiro Gabriela D. A. Guardia Shiva Ostadrahimi Erzsebet Kokovay Alexander Pertsemlidis Pedro A. F. Galante Luiz O. F. Penalva |
| author_sort | Adam Kosti |
| collection | DOAJ |
| description | Tumor suppressor microRNAs (miRNAs) have been explored as agents to target cancer stem cells. Most strategies use a single miRNA mimic and present many disadvantages, such as the amount of reagent required and the diluted effect on target genes. miRNAs work in a cooperative fashion to regulate distinct biological processes and pathways. Therefore, we propose that miRNA combinations could provide more efficient ways to target cancer stem cells. We have previously shown that miR-124, miR-128, and miR-137 function synergistically to regulate neurogenesis. We used a combination of these three miRNAs to treat glioma stem cells and showed that this treatment was much more effective than single miRNAs in disrupting cell proliferation and survival and promoting differentiation and response to radiation. Transcriptomic analyses indicated that transcription regulation, angiogenesis, metabolism, and neuronal differentiation are among the main biological processes affected by transfection of this miRNA combination. In conclusion, we demonstrated the value of using combinations of neurogenic miRNAs to disrupt cancer phenotypes and glioma stem cell growth. The synergistic effect of these three miRNA amplified the repression of oncogenic factors and the effect on cancer relevant pathways. Future therapeutic approaches would benefit from utilizing miRNA combinations, especially when targeting cancer-initiating cell populations. |
| first_indexed | 2024-03-09T04:47:59Z |
| format | Article |
| id | doaj.art-7922d9beaf274dfab3a1cc7a2c944a6d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:47:59Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7922d9beaf274dfab3a1cc7a2c944a6d2023-12-03T13:13:15ZengMDPI AGCancers2072-66942021-01-0113228910.3390/cancers13020289Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem CellsAdam Kosti0Rodrigo Barreiro1Gabriela D. A. Guardia2Shiva Ostadrahimi3Erzsebet Kokovay4Alexander Pertsemlidis5Pedro A. F. Galante6Luiz O. F. Penalva7Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USAGreehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USACentro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo 01308-060, BrazilGreehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADepartment of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USAGreehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USACentro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo 01308-060, BrazilGreehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USATumor suppressor microRNAs (miRNAs) have been explored as agents to target cancer stem cells. Most strategies use a single miRNA mimic and present many disadvantages, such as the amount of reagent required and the diluted effect on target genes. miRNAs work in a cooperative fashion to regulate distinct biological processes and pathways. Therefore, we propose that miRNA combinations could provide more efficient ways to target cancer stem cells. We have previously shown that miR-124, miR-128, and miR-137 function synergistically to regulate neurogenesis. We used a combination of these three miRNAs to treat glioma stem cells and showed that this treatment was much more effective than single miRNAs in disrupting cell proliferation and survival and promoting differentiation and response to radiation. Transcriptomic analyses indicated that transcription regulation, angiogenesis, metabolism, and neuronal differentiation are among the main biological processes affected by transfection of this miRNA combination. In conclusion, we demonstrated the value of using combinations of neurogenic miRNAs to disrupt cancer phenotypes and glioma stem cell growth. The synergistic effect of these three miRNA amplified the repression of oncogenic factors and the effect on cancer relevant pathways. Future therapeutic approaches would benefit from utilizing miRNA combinations, especially when targeting cancer-initiating cell populations.https://www.mdpi.com/2072-6694/13/2/289miRNAglioblastomaneuroblastomamiR-124miR-128miR-137 |
| spellingShingle | Adam Kosti Rodrigo Barreiro Gabriela D. A. Guardia Shiva Ostadrahimi Erzsebet Kokovay Alexander Pertsemlidis Pedro A. F. Galante Luiz O. F. Penalva Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells Cancers miRNA glioblastoma neuroblastoma miR-124 miR-128 miR-137 |
| title | Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells |
| title_full | Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells |
| title_fullStr | Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells |
| title_full_unstemmed | Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells |
| title_short | Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells |
| title_sort | synergism of proneurogenic mirnas provides a more effective strategy to target glioma stem cells |
| topic | miRNA glioblastoma neuroblastoma miR-124 miR-128 miR-137 |
| url | https://www.mdpi.com/2072-6694/13/2/289 |
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