| Autor: |
Yun-Hua Kuo, Huey-Shan Hung, Chia-Wen Tsai, Shao-Chih Chiu, Shih-Ping Liu, Yu-Ting Chiang, Woei-Cherng Shyu, Shinn-Zong Lin, Ru-Huei Fu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancers; Volume 14; Issue 16; Pages: 3890 |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers14163890 |
| Popis: |
Brain-enriched myelin-associated protein 1 (BCAS1) is frequently highly expressed in human cancer, but its detailed function is unclear. Here, we identified a novel splice variant of the BCAS1 gene in glioblastoma multiforme (GBM) named BCAS1-SV1. The expression of BCAS1-SV1 was weak in heathy brain cells but high in GBM cell lines. The overexpression of BCAS1-SV1 significantly increased the proliferation and migration of GBM cells, whereas the RNA-interference-mediated knockdown of BCAS1-SV1 reduced proliferation and migration. Moreover, using a yeast-two hybrid assay, immunoprecipitation, and immunofluorescence staining, we confirmed that β-arrestin 2 is an interaction partner of BCAS1-SV1 but not BCAS1. The downregulation of β-arrestin 2 directly enhanced the malignancy of GBM and abrogated the effects of BCAS1-SV1 on GBM cells. Finally, we used a yeast two-hybrid-based growth assay to identify that maackiain (MK) is a potential inhibitor of the interaction between BCAS1-SV1 and β-arrestin 2. MK treatment lessened the proliferation and migration of GBM cells and prolonged the lifespan of tumor-bearing mice in subcutaneous xenograft and intracranial U87-luc xenograft models. This study provides the first evidence that the gain-of-function BCAS1-SV1 splice variant promotes the development of GBM by suppressing the β-arrestin 2 pathway and opens up a new therapeutic perspective in GBM. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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