A Novel Splice Variant of BCAS1 Inhibits ?-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain.

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 ?-arrestin 2 is an interaction partner of BCAS1-SV1 but not BCAS1. The downregulation of ?-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 ?-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 ?-arrestin 2 pathway and opens up a new therapeutic perspective in GBM.
Cancers (Basel)
Date: Aug. 11, 2022
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