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Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we clon...

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Autores principales: Fu, Ru-Huei, Hong, Syuan-Yu, Tsai, Chia-Wen, Liu, Shih-Ping, Chiu, Shao-Chih, Wu, Meng-Zhen, Shyu, Woei-Cherng, Lin, Shinn-Zong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047488/
https://www.ncbi.nlm.nih.gov/pubmed/36980235
http://dx.doi.org/10.3390/cells12060894
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author Fu, Ru-Huei
Hong, Syuan-Yu
Tsai, Chia-Wen
Liu, Shih-Ping
Chiu, Shao-Chih
Wu, Meng-Zhen
Shyu, Woei-Cherng
Lin, Shinn-Zong
author_facet Fu, Ru-Huei
Hong, Syuan-Yu
Tsai, Chia-Wen
Liu, Shih-Ping
Chiu, Shao-Chih
Wu, Meng-Zhen
Shyu, Woei-Cherng
Lin, Shinn-Zong
author_sort Fu, Ru-Huei
collection PubMed
description Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-β dehydrogenase 1 like gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.
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spelling pubmed-100474882023-03-29 Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction Fu, Ru-Huei Hong, Syuan-Yu Tsai, Chia-Wen Liu, Shih-Ping Chiu, Shao-Chih Wu, Meng-Zhen Shyu, Woei-Cherng Lin, Shinn-Zong Cells Article Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-β dehydrogenase 1 like gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment. MDPI 2023-03-14 /pmc/articles/PMC10047488/ /pubmed/36980235 http://dx.doi.org/10.3390/cells12060894 Text en © 2023 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
Fu, Ru-Huei
Hong, Syuan-Yu
Tsai, Chia-Wen
Liu, Shih-Ping
Chiu, Shao-Chih
Wu, Meng-Zhen
Shyu, Woei-Cherng
Lin, Shinn-Zong
Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title_full Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title_fullStr Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title_full_unstemmed Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title_short Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction
title_sort interaction of a novel alternatively spliced variant of hsd11b1l with parkin enhances the carcinogenesis potential of glioblastoma: peiminine interferes with this interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047488/
https://www.ncbi.nlm.nih.gov/pubmed/36980235
http://dx.doi.org/10.3390/cells12060894
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