Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> 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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MDPI AG
2023-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/894 |
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| author | Ru-Huei Fu Syuan-Yu Hong Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Meng-Zhen Wu Woei-Cherng Shyu Shinn-Zong Lin |
| author_facet | Ru-Huei Fu Syuan-Yu Hong Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Meng-Zhen Wu Woei-Cherng Shyu Shinn-Zong Lin |
| author_sort | Ru-Huei Fu |
| collection | DOAJ |
| 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 (<i>HSD11B1L</i>) 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 <i>Fritillaria thunbergii</i> 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. |
| first_indexed | 2024-03-11T06:47:29Z |
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| language | English |
| last_indexed | 2024-03-11T06:47:29Z |
| publishDate | 2023-03-01 |
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| series | Cells |
| spelling | doaj.art-3a5ec51c1b004aff9da254c080f694822023-11-17T10:13:21ZengMDPI AGCells2073-44092023-03-0112689410.3390/cells12060894Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This InteractionRu-Huei Fu0Syuan-Yu Hong1Chia-Wen Tsai2Shih-Ping Liu3Shao-Chih Chiu4Meng-Zhen Wu5Woei-Cherng Shyu6Shinn-Zong Lin7Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanDepartment of Nutrition, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanBuddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien 97002, TaiwanGlioblastoma (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 (<i>HSD11B1L</i>) 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 <i>Fritillaria thunbergii</i> 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.https://www.mdpi.com/2073-4409/12/6/894glioblastomaalternative splicinghydroxysteroid 11-β-dehydrogenase 1 like gene (HSD11B1L)proliferationmigrationinvasion |
| spellingShingle | Ru-Huei Fu Syuan-Yu Hong Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Meng-Zhen Wu Woei-Cherng Shyu Shinn-Zong Lin Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction Cells glioblastoma alternative splicing hydroxysteroid 11-β-dehydrogenase 1 like gene (HSD11B1L) proliferation migration invasion |
| title | Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction |
| title_full | Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction |
| title_fullStr | Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction |
| title_full_unstemmed | Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction |
| title_short | Interaction of a Novel Alternatively Spliced Variant of <i>HSD11B1L</i> with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction |
| title_sort | interaction of a novel alternatively spliced variant of i hsd11b1l i with parkin enhances the carcinogenesis potential of glioblastoma peiminine interferes with this interaction |
| topic | glioblastoma alternative splicing hydroxysteroid 11-β-dehydrogenase 1 like gene (HSD11B1L) proliferation migration invasion |
| url | https://www.mdpi.com/2073-4409/12/6/894 |
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