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Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis
SIMPLE SUMMARY: The prognosis of high-risk neuroblastoma is poor due to its high relapse rate. To date, no effective treatment for this disease has been developed. In this study, we utilized two neuroblastoma cell lines (IMR-5 and SK-N-AS) as a model system to explore the effects of cannabinol (CBN)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027424/ https://www.ncbi.nlm.nih.gov/pubmed/35454815 http://dx.doi.org/10.3390/cancers14081908 |
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author | Wang, Bo Li, Dongping Cherkasova, Viktoriia Gerasymchuk, Marta Narendran, Aru Kovalchuk, Igor Kovalchuk, Olga |
author_facet | Wang, Bo Li, Dongping Cherkasova, Viktoriia Gerasymchuk, Marta Narendran, Aru Kovalchuk, Igor Kovalchuk, Olga |
author_sort | Wang, Bo |
collection | PubMed |
description | SIMPLE SUMMARY: The prognosis of high-risk neuroblastoma is poor due to its high relapse rate. To date, no effective treatment for this disease has been developed. In this study, we utilized two neuroblastoma cell lines (IMR-5 and SK-N-AS) as a model system to explore the effects of cannabinol (CBN) on neuroblastoma and elucidate the potential mechanisms of action. We reveal an inhibitory role of CBN on neuroblastoma cell proliferation, invasion, and angiogenesis through miR-34a-mediated targeting. We identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) as a direct target of a novel 31 nt tRNA(i)(Met) fragment tRiMetF31 generated from miR-34a-guided cleavage, highlighting the crucial role of the miR-34a/tRiMetF31/PFKFB3 axis in CBN-mediated suppression in neuroblastoma biology. ABSTRACT: High-risk neuroblastoma is an aggressive pediatric tumor. Despite great advances in neuroblastoma therapy and supportive care protocols, no curative treatment is available for most patients with this disease. Here, we uncover that CBN attenuated the cell proliferation, invasion, and angiogenesis of neuroblastoma cell lines in a dose-dependent manner via the inhibition of the AKT pathway and the upregulation of miR-34a that targets E2F1. Both miR-34a and a 31-nt tRNA(i)(Met) fragment (tRiMetF31) derived from miR-34a-guided cleavage were downregulated in 4 examined neuroblastoma cell lines inversely correlated with the levels of its direct target, the PFKFB3 protein. Moreover, ectopic tRiMetF31 suppressed proliferation, migration, and angiogenesis in the studied neuroblastoma cell lines. Conversely, tRiMetF31 knockdown promoted PFKFB3 expression, resulting in enhanced angiogenesis. Our findings reveal a suppressive role of CBN in neuroblastoma tumorigenesis, highlighting a novel and crucial miR-34a tumor suppressor network in CBN’s antineuroblastoma actions. |
format | Online Article Text |
id | pubmed-9027424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90274242022-04-23 Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis Wang, Bo Li, Dongping Cherkasova, Viktoriia Gerasymchuk, Marta Narendran, Aru Kovalchuk, Igor Kovalchuk, Olga Cancers (Basel) Article SIMPLE SUMMARY: The prognosis of high-risk neuroblastoma is poor due to its high relapse rate. To date, no effective treatment for this disease has been developed. In this study, we utilized two neuroblastoma cell lines (IMR-5 and SK-N-AS) as a model system to explore the effects of cannabinol (CBN) on neuroblastoma and elucidate the potential mechanisms of action. We reveal an inhibitory role of CBN on neuroblastoma cell proliferation, invasion, and angiogenesis through miR-34a-mediated targeting. We identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) as a direct target of a novel 31 nt tRNA(i)(Met) fragment tRiMetF31 generated from miR-34a-guided cleavage, highlighting the crucial role of the miR-34a/tRiMetF31/PFKFB3 axis in CBN-mediated suppression in neuroblastoma biology. ABSTRACT: High-risk neuroblastoma is an aggressive pediatric tumor. Despite great advances in neuroblastoma therapy and supportive care protocols, no curative treatment is available for most patients with this disease. Here, we uncover that CBN attenuated the cell proliferation, invasion, and angiogenesis of neuroblastoma cell lines in a dose-dependent manner via the inhibition of the AKT pathway and the upregulation of miR-34a that targets E2F1. Both miR-34a and a 31-nt tRNA(i)(Met) fragment (tRiMetF31) derived from miR-34a-guided cleavage were downregulated in 4 examined neuroblastoma cell lines inversely correlated with the levels of its direct target, the PFKFB3 protein. Moreover, ectopic tRiMetF31 suppressed proliferation, migration, and angiogenesis in the studied neuroblastoma cell lines. Conversely, tRiMetF31 knockdown promoted PFKFB3 expression, resulting in enhanced angiogenesis. Our findings reveal a suppressive role of CBN in neuroblastoma tumorigenesis, highlighting a novel and crucial miR-34a tumor suppressor network in CBN’s antineuroblastoma actions. MDPI 2022-04-10 /pmc/articles/PMC9027424/ /pubmed/35454815 http://dx.doi.org/10.3390/cancers14081908 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Bo Li, Dongping Cherkasova, Viktoriia Gerasymchuk, Marta Narendran, Aru Kovalchuk, Igor Kovalchuk, Olga Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title | Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title_full | Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title_fullStr | Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title_full_unstemmed | Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title_short | Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis |
title_sort | cannabinol inhibits cellular proliferation, invasion, and angiogenesis of neuroblastoma via novel mir-34a/trimetf31/pfkfb3 axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027424/ https://www.ncbi.nlm.nih.gov/pubmed/35454815 http://dx.doi.org/10.3390/cancers14081908 |
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