Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784805916510519296 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9550604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT guxiao prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT hemiao prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT lebedevtimofey prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT linchenghan prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT huazhongyan prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT zhengygeorge prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT lizhijie prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT yangjeryen prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival AT lixingguo prmt1isanimportantfactorformedulloblastomacellproliferationandsurvival |