CBL proto-oncogene C-mediated synaptophysin 1 regulates prostate cancer progression in the TGF-beta signalling...

This study aims to screen and validate the differentially expressed gene synaptophysin 1 (SYT1), which plays a key regulatory role in prostate cancer, explore its function and potential regulatory mechanisms, and clarify its biological role and molecular mechanisms in the malignant progression of prostate cancer.

Differential expression analysis was performed using the GEO database dataset GSE69223, combined with the TIMER and UALCAN databases to validate the expression levels and prognostic value of the candidate gene SYT1. To further ensure the biological plausibility of the results, this study selected cell lines representing different prostate cancer subtypes and disease stages, including the normal epithelial cell line RWPE-1, the adenocarcinoma-like AR⁺ cell line LNCaP, the basal-like/AR⁻ cell line PC3, and the neuroendocrine cell line NCI-H660, and assessed differences in SYT1 expression using qRT-PCR and Western blot analysis. SYT1-overexpressing cell lines were established, and their effects on prostate cancer cell proliferation, migration, and invasion were assessed using EDU, colony formation, scratch, and Transwell assays. Using UbiBrowser, we predicted potential E3 ubiquitin ligases for SYT1 and screened CBL proto-oncogene C (CBLC) as a candidate upstream regulatory factor through differential analysis. We validated the regulatory role of CBLC in SYT1 ubiquitination and degradation via immunoprecipitation experiments and explored its mechanism of action through functional interaction experiments and signalling pathway analysis.

SYT1 is significantly downregulated in prostate cancer tissues, and its downregulation is associated with poor prognosis in prostate cancer. Overexpression of SYT1 significantly inhibits the proliferation, migration, and invasion of prostate cancer cells. CBLC is highly expressed in prostate cancer and promotes the ubiquitination and degradation of SYT1. Knocking down CBLC reduces the ubiquitination level of SYT1 and stabilises its protein expression. Overexpression of CBLC partially reverses the antitumour effects mediated by SYT1. Mechanistic studies indicate that SYT1 exerts its antitumour function by inhibiting the TGF-β/SMAD signalling pathway, while CBLC interferes with this pathway by promoting its degradation.

Prostate cancer may have SYT1 as a tumor suppressor gene, and the E3 ligase CBLC regulates its ubiquitin-mediated degradation. SYT1 inhibits tumour progression by suppressing the TGF-β/SMAD signalling pathway, while CBLC promotes the malignant development of prostate cancer by negatively regulating SYT1.