Zhang X, Wu H, Wang S
Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Sep 20;43(9):1613-1621. doi: 10.12122/j.issn.1673-4254.2023.09.20.
To investigate the role of solute carrier family 12 member A8 (SLC12A8) in regulation of biological behaviors of bladder cancer and the mechanism mediating its effect.
The TCGA database was used to analyze SLC12A8 expression in bladder cancer and is correlation with prognosis and clinicopathological characteristics of the patients. In different bladder cancer cell lines, the effects of transient transfection with SLC12A8 siRNA on cell proliferation, invasion and migration ability were examined using CCK-8 assay, Transwell assay and scratch experiment. Gene set enrichment analysis (GSEA) was carried out to analyze pathway enrichment. The correlation of SLC12A8 with the expressions of epithelial-mesenchymal transition (EMT) markers was analyzed using Western blotting. The effect of colivelin on biological behaviors of the cells with SLC12A8 knockdown was assessed using CCK-8 and Transwell assays.
SLC12A8 was highly expressed in bladder cancer (<0.05) and associated with a poor prognosis and advanced pathological stages of the patients (<0.05), and could serve as an independent prognostic factor. The bladder cancer cell lines with SLC12A8 knockdown showed significantly attenuated proliferation, invasion and migration capacities (<0.05). GSEA identified significant gene enrichment in the JAK/STAT signaling pathway (=0.008). Correlation analysis showed that SLC12A8 expression was negatively correlated with E- cadherin expression (=-0.167, <0.001) but positively with N-cadherin (=0.306, <0.001) and vimentin (=0.358, <0.001) expressions. The bladder cancer cells with SLC12A8 knockdown showed significantly decreased expressions of p-Jak2, p-Stat3, N-cadherin and vimentin proteins with an increased expression of E-cadherin. Treatment with colivelin effectively enhanced proliferation, invasion and migration capacities of the bladder cancer cells with SLC12A8 knockdown (<0.05).
SLC12A8 promotes bladder cancer progression by activating the JAK/STAT signaling pathway and its high expression is closely associated with a poor prognosis of the patients.
探讨溶质载体家族12成员A8（SLC12A8）在膀胱癌生物学行为调控中的作用及其作用机制。
利用TCGA数据库分析SLC12A8在膀胱癌中的表达及其与患者预后和临床病理特征的相关性。在不同的膀胱癌细胞系中，采用CCK-8法、Transwell法和划痕实验检测SLC12A8 siRNA瞬时转染对细胞增殖、侵袭和迁移能力的影响。进行基因集富集分析（GSEA）以分析通路富集情况。采用蛋白质免疫印迹法分析SLC12A8与上皮-间质转化（EMT）标志物表达的相关性。使用CCK-8法和Transwell法评估colivelin对SLC12A8基因敲低细胞生物学行为的影响。
SLC12A8在膀胱癌中高表达（P<0.05），与患者预后不良和病理分期较晚相关（P<0.05），可作为独立的预后因素。SLC12A8基因敲低的膀胱癌细胞系增殖、侵袭和迁移能力明显减弱（P<0.05）。GSEA分析显示JAK/STAT信号通路存在显著基因富集（P=0.008）。相关性分析表明，SLC12A8表达与E-钙黏蛋白表达呈负相关（r=-0.167，P<0.001），与N-钙黏蛋白（r=0.306，P<0.001）和波形蛋白（r=0.358，P<0.001）表达呈正相关。SLC12A8基因敲低的膀胱癌细胞中，p-Jak2、p-Stat3、N-钙黏蛋白和波形蛋白蛋白表达显著降低，E-钙黏蛋白表达增加。colivelin处理可有效增强SLC12A8基因敲低的膀胱癌细胞的增殖、侵袭和迁移能力（P<0.05）。
SLC12A8通过激活JAK/STAT信号通路促进膀胱癌进展，其高表达与患者预后不良密切相关。
