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- W4280526779 abstract "Alternative splicing of mRNA precursors allows cancer cells to create different protein isoforms that promote growth and survival. Compared to normal cells, cancer cells frequently exhibit a higher diversity of their transcriptomes. A comprehensive understanding of splicing regulation is required to correct the splicing alterations for the future precision oncology. A quantitative proteomic screen was performed to identify the regulators associated the metastasis in triple-negative breast cancer. Multiple in vitro and in vivo functional analyses were used to study the effects of NSrp70 on breast cancer metastasis. Next, transcriptomic sequencing (RNA-seq) and alternative splicing bioinformatics analysis was applied to screen the potential targets of NSrp70. Moreover, in vitro splicing assays, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the specific binding between NSrp70 and downstream target genes. Furthermore, the prognostic value of NSrp70 was analyzed in a cohort of patients by performing IHC. We uncovered NSrp70 as a novel suppressor of breast cancer metastasis. We discovered that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of transforming growth factor receptor 1 through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with a better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 serves as a metastasis suppressor." @default.
- W4280526779 created "2022-05-22" @default.
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- W4280526779 date "2022-05-14" @default.
- W4280526779 modified "2023-09-26" @default.
- W4280526779 title "NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis" @default.
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- W4280526779 doi "https://doi.org/10.1038/s41388-022-02349-z" @default.
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