<i>Downregulation of BUD31</i> Promotes Prostate Cancer Cell Proliferation and Migration via Activation of p-AKT and Vimentin In Vitro
Among men, prostate cancer (PCa) is the second most frequently diagnosed cancer subtype and has demonstrated a high degree of prevalence globally. BUD31, also known as Functional Spliceosome-Associated Protein 17, is a protein that works at the level of the spliceosome; it is functionally implicated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6055 |
| Summary: | Among men, prostate cancer (PCa) is the second most frequently diagnosed cancer subtype and has demonstrated a high degree of prevalence globally. BUD31, also known as Functional Spliceosome-Associated Protein 17, is a protein that works at the level of the spliceosome; it is functionally implicated in pre-mRNA splicing as well as processing, while also acting as a transcriptional regulator of androgen receptor (AR) target genes. Clinically, the expression of <i>BUD31</i> and its functions in the development and progression of PCa is yet to be elucidated. The BUD31 expression was assessed using IHC in a tissue microarray (TMA) constructed from a cohort of 284 patient samples. In addition, we analyzed the prostate adenocarcinoma (TCGAPRAD-) database. Finally, we used PCa cell lines to knockdown <i>BUD31</i> to study the underlying mechanisms in vitro.Assesment of BUD31 protein expression revealed lower expression in incidental and advanced PCa, and significantly lower expression was observed in patients diagnosed with castrate-resistant prostate cancer. Additionally, bioinformatic analysis and GSEA revealed that <i>BUD31</i> increased processes related to cancer cell migration and proliferation. In vitro results made evident that <i>BUD31</i> knockdown in PC3 cells led to an increase in the G2 cell population, indicating a more active and proliferative state. Additionally, an investigation of metastatic processes revealed that knockdown of <i>BUD31</i> significantly enhanced the ability of PC3 cells to migrate and invade. Our in vitro results showed <i>BUD31</i> knockdown promotes cell proliferation and migration of prostate cancer cells via activation of p-AKT and vimentin. These results support the clinical data, where low expression of BUD31 was correlated to more advanced stages of PCa. |
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| ISSN: | 1661-6596 1422-0067 |