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PRMT1 is an important factor for medulloblastoma cell proliferation and survival

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor co...

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Autores principales: Gu, Xiao, He, Miao, Lebedev, Timofey, Lin, Cheng-Han, Hua, Zhong-Yan, Zheng, Y. George, Li, Zhi-Jie, Yang, Jer-Yen, Li, Xing-Guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550604/
https://www.ncbi.nlm.nih.gov/pubmed/36237442
http://dx.doi.org/10.1016/j.bbrep.2022.101364
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author Gu, Xiao
He, Miao
Lebedev, Timofey
Lin, Cheng-Han
Hua, Zhong-Yan
Zheng, Y. George
Li, Zhi-Jie
Yang, Jer-Yen
Li, Xing-Guo
author_facet Gu, Xiao
He, Miao
Lebedev, Timofey
Lin, Cheng-Han
Hua, Zhong-Yan
Zheng, Y. George
Li, Zhi-Jie
Yang, Jer-Yen
Li, Xing-Guo
author_sort Gu, Xiao
collection PubMed
description Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor collection, we found that PRMT1 was predominantly expressed in medulloblastomas across all the pediatric brain tumors and that the high-level expression of PRMT1 correlated with poor survival of medulloblastoma patients. To determine the role of PRMT1 in medulloblastoma cells, we established an inducible knockdown system and demonstrated that PRMT1 depletion decreased medulloblastoma cell proliferation and induced cell apoptosis. Furthermore, the diamidine compounds, previously shown to exhibit selective PRMT1 inhibition, suppressed medulloblastoma cell viability in a dose-dependent manner. Finally, we observed induction of medulloblastoma cell apoptosis by the potent diamidine compounds at low micromolar concentrations. Together, our results suggest that PRMT1 could be an actionable therapeutic target in medulloblastoma.
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spelling pubmed-95506042022-10-12 PRMT1 is an important factor for medulloblastoma cell proliferation and survival Gu, Xiao He, Miao Lebedev, Timofey Lin, Cheng-Han Hua, Zhong-Yan Zheng, Y. George Li, Zhi-Jie Yang, Jer-Yen Li, Xing-Guo Biochem Biophys Rep Research Article Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor collection, we found that PRMT1 was predominantly expressed in medulloblastomas across all the pediatric brain tumors and that the high-level expression of PRMT1 correlated with poor survival of medulloblastoma patients. To determine the role of PRMT1 in medulloblastoma cells, we established an inducible knockdown system and demonstrated that PRMT1 depletion decreased medulloblastoma cell proliferation and induced cell apoptosis. Furthermore, the diamidine compounds, previously shown to exhibit selective PRMT1 inhibition, suppressed medulloblastoma cell viability in a dose-dependent manner. Finally, we observed induction of medulloblastoma cell apoptosis by the potent diamidine compounds at low micromolar concentrations. Together, our results suggest that PRMT1 could be an actionable therapeutic target in medulloblastoma. Elsevier 2022-10-06 /pmc/articles/PMC9550604/ /pubmed/36237442 http://dx.doi.org/10.1016/j.bbrep.2022.101364 Text en © 2022 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Gu, Xiao
He, Miao
Lebedev, Timofey
Lin, Cheng-Han
Hua, Zhong-Yan
Zheng, Y. George
Li, Zhi-Jie
Yang, Jer-Yen
Li, Xing-Guo
PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title_full PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title_fullStr PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title_full_unstemmed PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title_short PRMT1 is an important factor for medulloblastoma cell proliferation and survival
title_sort prmt1 is an important factor for medulloblastoma cell proliferation and survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550604/
https://www.ncbi.nlm.nih.gov/pubmed/36237442
http://dx.doi.org/10.1016/j.bbrep.2022.101364
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