Cargando…

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)...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Bo, Li, Dongping, Cherkasova, Viktoriia, Gerasymchuk, Marta, Narendran, Aru, Kovalchuk, Igor, Kovalchuk, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784691359328763904
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
work_keys_str_mv AT wangbo cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT lidongping cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT cherkasovaviktoriia cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT gerasymchukmarta cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT narendranaru cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT kovalchukigor cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis
AT kovalchukolga cannabinolinhibitscellularproliferationinvasionandangiogenesisofneuroblastomavianovelmir34atrimetf31pfkfb3axis