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Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: SLC12A8 was highly expressed in bladder cancer (P<0.05) and associated with a poor prognosis and advanced pathological stages of the patients (P<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 (P<0.05). GSEA identified significant gene enrichment in the JAK/STAT signaling pathway (P=0.008). Correlation analysis showed that SLC12A8 expression was negatively correlated with E- cadherin expression (r=-0.167, P<0.001) but positively with N-cadherin (r=0.306, P<0.001) and vimentin (r=0.358, P<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 (P<0.05).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: SLC12A8 was highly expressed in bladder cancer (P<0.05) and associated with a poor prognosis and advanced pathological stages of the patients (P<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 (P<0.05). GSEA identified significant gene enrichment in the JAK/STAT signaling pathway (P=0.008). Correlation analysis showed that SLC12A8 expression was negatively correlated with E- cadherin expression (r=-0.167, P<0.001) but positively with N-cadherin (r=0.306, P<0.001) and vimentin (r=0.358, P<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 (P<0.05).
CONCLUSIONS: 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.
摘要：
目的：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介导机制。
方法：TCGA数据库用于分析SLC12A8在膀胱癌中的表达，并与患者的预后和临床病理特征相关。在不同的膀胱癌细胞系中，SLC12A8siRNA瞬时转染对细胞增殖的影响,使用CCK-8测定法检查侵袭和迁移能力，Transwell测定和划痕实验。进行基因集富集分析(GSEA)以分析途径富集。使用Westernblotting分析SLC12A8与上皮-间质转化（EMT）标志物表达的相关性。使用CCK-8和Transwell测定来评估柯里维林对具有SLC12A8敲低的细胞的生物学行为的影响。
结果：SLC12A8在膀胱癌中高表达（P<0.05），与患者预后不良和晚期病理分期有关（P<0.05）。并可作为独立的预后因素。SLC12A8敲低的膀胱癌细胞株增殖明显减弱,侵袭和迁移能力(P<0.05)。GSEA鉴定了JAK/STAT信号通路中显著的基因富集(P=0.008)。相关分析显示,SLC12A8的表达与E-cadherin的表达呈负相关(r=-0.167,P<0.001),与N-cadherin的表达呈正相关(r=0.306,P<0.001),与波形蛋白的表达呈正相关(r=0.358,P<0.001)。SLC12A8敲低的膀胱癌细胞显示p-Jak2，p-Stat3，N-cadherin和波形蛋白的表达显着降低，而E-cadherin的表达增加。用Colivelin治疗可有效增强增殖，SLC12A8敲低膀胱癌细胞的侵袭和迁移能力(P<0.05)。
结论：SLC12A8通过激活JAK/STAT信号通路促进膀胱癌进展，其高表达与患者不良预后密切相关。
方法：TCGA数据库用于分析SLC12A8在膀胱癌中的表达，并与患者的预后和临床病理特征相关。在不同的膀胱癌细胞系中，SLC12A8siRNA瞬时转染对细胞增殖的影响,使用CCK-8测定法检查侵袭和迁移能力，Transwell测定和划痕实验。进行基因集富集分析(GSEA)以分析途径富集。使用Westernblotting分析SLC12A8与上皮-间质转化（EMT）标志物表达的相关性。使用CCK-8和Transwell测定来评估柯里维林对具有SLC12A8敲低的细胞的生物学行为的影响。
结果：SLC12A8在膀胱癌中高表达（P<0.05），与患者预后不良和晚期病理分期有关（P<0.05）。并可作为独立的预后因素。SLC12A8敲低的膀胱癌细胞株增殖明显减弱,侵袭和迁移能力(P<0.05)。GSEA鉴定了JAK/STAT信号通路中显著的基因富集(P=0.008)。相关分析显示,SLC12A8的表达与E-cadherin的表达呈负相关(r=-0.167,P<0.001),与N-cadherin的表达呈正相关(r=0.306,P<0.001),与波形蛋白的表达呈正相关(r=0.358,P<0.001)。SLC12A8敲低的膀胱癌细胞显示p-Jak2，p-Stat3，N-cadherin和波形蛋白的表达显着降低，而E-cadherin的表达增加。用Colivelin治疗可有效增强增殖，SLC12A8敲低膀胱癌细胞的侵袭和迁移能力(P<0.05)。
结论：SLC12A8通过激活JAK/STAT信号通路促进膀胱癌进展，其高表达与患者不良预后密切相关。
