CRISPR-Cas knockout of miR21 reduces glioma growth
Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Cell Press
2022
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| _version_ | 1825938444164005888 |
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| author | Nieland, Lisa Solinge, Thomas S. van Cheah, Pike See Morsett, Liza M. Khoury, Joseph El Rissman, Joseph I. Kleinstiver, Benjamin P. Broekman, Marike L. D. Breakefield, Xandra O. Abels, Erik R. |
| author_facet | Nieland, Lisa Solinge, Thomas S. van Cheah, Pike See Morsett, Liza M. Khoury, Joseph El Rissman, Joseph I. Kleinstiver, Benjamin P. Broekman, Marike L. D. Breakefield, Xandra O. Abels, Erik R. |
| author_sort | Nieland, Lisa |
| collection | UPM |
| description | Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion, and proliferation in vitro. In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both in vitro and in vivo. Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma. |
| first_indexed | 2024-03-06T11:13:57Z |
| format | Article |
| id | upm.eprints-100836 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-03-06T11:13:57Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | upm.eprints-1008362023-08-22T03:45:44Z http://psasir.upm.edu.my/id/eprint/100836/ CRISPR-Cas knockout of miR21 reduces glioma growth Nieland, Lisa Solinge, Thomas S. van Cheah, Pike See Morsett, Liza M. Khoury, Joseph El Rissman, Joseph I. Kleinstiver, Benjamin P. Broekman, Marike L. D. Breakefield, Xandra O. Abels, Erik R. Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion, and proliferation in vitro. In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both in vitro and in vivo. Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma. Cell Press 2022-04-06 Article PeerReviewed Nieland, Lisa and Solinge, Thomas S. van and Cheah, Pike See and Morsett, Liza M. and Khoury, Joseph El and Rissman, Joseph I. and Kleinstiver, Benjamin P. and Broekman, Marike L. D. and Breakefield, Xandra O. and Abels, Erik R. (2022) CRISPR-Cas knockout of miR21 reduces glioma growth. Molecular Therapy: Oncolytics, 25. 121 - 136. ISSN 2372-7705 https://www.cell.com/molecular-therapy-family/oncolytics/fulltext/S2372-7705(22)00053-5# 10.1016/j.omto.2022.04.001 |
| spellingShingle | Nieland, Lisa Solinge, Thomas S. van Cheah, Pike See Morsett, Liza M. Khoury, Joseph El Rissman, Joseph I. Kleinstiver, Benjamin P. Broekman, Marike L. D. Breakefield, Xandra O. Abels, Erik R. CRISPR-Cas knockout of miR21 reduces glioma growth |
| title | CRISPR-Cas knockout of miR21 reduces glioma growth |
| title_full | CRISPR-Cas knockout of miR21 reduces glioma growth |
| title_fullStr | CRISPR-Cas knockout of miR21 reduces glioma growth |
| title_full_unstemmed | CRISPR-Cas knockout of miR21 reduces glioma growth |
| title_short | CRISPR-Cas knockout of miR21 reduces glioma growth |
| title_sort | crispr cas knockout of mir21 reduces glioma growth |
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