King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia.
Int J Mol Sci. 2023 Oct 30;24(21):15763. doi: 10.3390/ijms242115763.
The involvement of the actin-regulatory protein, gelsolin (GSN), in neoplastic transformation has been reported in different cancers including bladder cancer. However, the exact mechanism by which GSN influences bladder cancer development is not well understood. Here, we sought to reveal the functional significance of GSN in bladder cancer by undertaking a comprehensive bioinformatic analysis of TCGA datasets and through the assessment of multiple biological functions. GSN expression was knocked down in bladder cancer cell lines with two siRNA isoforms targeting GSN. Proliferation, migration, cell cycle and apoptosis assays were carried out. GSN expression, enrichment analysis, protein-protein interaction and immune infiltration analysis were verified through online TCGA tools. The data indicated that GSN expression is associated with bladder cancer proliferation, migration and enhanced cell apoptosis through regulation of NF-κB expression. GSN expression correlated with various inflammatory cells and may influence the immunity of the tumor microenvironment. Computational analysis identified several interacting partners which are associated with cancer progression and patient outcome. The present results demonstrate that GSN plays an important role in bladder cancer pathogenesis and may serve as a potential biomarker and therapeutic target for cancer therapy.
肌动蛋白调节蛋白gelsolin (GSN) 参与肿瘤转化已在包括膀胱癌在内的不同癌症中报道。然而，GSN 影响膀胱癌发展的确切机制尚不清楚。在这里，我们通过对 TCGA 数据集进行全面的生物信息学分析以及评估多种生物学功能，试图揭示 GSN 在膀胱癌中的功能意义。我们使用两种针对 GSN 的 siRNA 同种型敲低了膀胱癌细胞系中的 GSN 表达。进行了增殖、迁移、细胞周期和凋亡测定。通过在线 TCGA 工具验证了 GSN 表达、富集分析、蛋白质-蛋白质相互作用和免疫浸润分析。数据表明，GSN 表达通过调节 NF-κB 表达与膀胱癌增殖、迁移和增强细胞凋亡相关。GSN 表达与各种炎症细胞相关，可能影响肿瘤微环境的免疫。计算分析确定了与癌症进展和患者预后相关的几个相互作用伙伴。本研究结果表明，GSN 在膀胱癌发病机制中发挥重要作用，可能成为癌症治疗的潜在生物标志物和治疗靶点。
