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The potential biological function of STARD8 in prostate cancer: A bioinformatic and experimental validation study

Year: 2025

Type: article

Abstract: BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignancies among men, with its incidence and mortality rates rising globally, posing a significant threat to men's health. STARD8, an emerging tumor suppressor gene, has been reported to inhibit cancer cell proliferation and migration in certain cancers. However, its role in PCa remains inadequately understood. METHODS: Bioinformatic analyses utilizing the TCGA, GTEx, and MSigDB databases were conducted to investigate the biological functions of STARD8. Differential expression of STARD8 was confirmed through immunohistochemistry, western blotting (WB), and quantitative PCR (Q-PCR) using clinical samples and cell lines. Functional assays, including STARD8 silencing and overexpression in PC3, DU145, C4-2B, LNCaP and WPMY-1 cells, were performed using immunofluorescence staining, WB, EdU assays, and comet assays. RESULTS: Transcriptomic data and clinical samples revealed that STARD8 expression is significantly reduced in PCa. In PCa cells, silencing STARD8 enhanced cell adhesion, migration, and invasion, whereas overexpression of STARD8 significantly suppressed these processes. Furthermore, STARD8 expression was found to be closely associated with immune evasion and drug sensitivity in PCa. Functional assays demonstrated that upregulation of STARD8 in PCa cells enhanced the chemotherapeutic efficacy of cisplatin. Mechanistically, STARD8 negatively regulated total FAK and p-FAK protein levels, thereby modulating PCa cell migration, proliferation, immune responses, and drug sensitivity. CONCLUSION: This study identifies STARD8 as a critical tumor suppressor with significant roles in regulating cell proliferation, migration, immune evasion, and drug sensitivity in tumors.

Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI: 10.1016/j.bbadis.2025.167897