Yu Chengqing, Li Haoran, Zhang Chen, Tang Yuchen, Huang Yujie, Lu Haodong, Jin Kanghui, Zhou Jian, Yang Jian
Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Department of Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
Discov Oncol. 2024 Oct 28;15(1):597. doi: 10.1007/s12672-024-01488-x.
Solute Carrier Family 4 Member 4 (SLC4A4) is a membrane protein-coding gene for a Na/HCO cotransporter and plays a crucial role in regulating pH, bicarbonate secretion and homeostasis. However, the prognostic and immunological role of SLC4A4 in colon cancer remains unknown.
In this study, expression profiles of SLC4A4 were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, to which a variety of bioinformatic analyses were performed. Sangerbox, Xiantao, ESTIMATE and TIMER online tools were used to delve into the relationship between SLC4A4 expression and immune cell infiltration. The role of SLC4A4 in the proliferation and migration of colon cancer cells was verified by CCK8, EdU and wound healing assays. The related molecules and pathways that SLC4A4 may affect were validated by bioinformatic prediction and western blotting analysis.
The expression levels of SLC4A4 were significantly lower in colon cancer tissues than in normal tissues and its low expression was positively correlated with poor prognosis. TIMER and ESTIMATE showed that SLC4A4 broadly influenced immune cell infiltration. Experiments in vitro demonstrated that SLC4A4 inhibited partial epithelial-mesenchymal transition (EMT) phenotypes.
To conclude, our study revealed that SLC4A4 is lowly expressed in colon cancer tissues, and SLC4A4 may inhibit the progression of colon cancer via regulating partial EMT phenotypes and immune cell infiltration, which may provide new perspectives for the development of more precise and personalized immune anti-tumor therapies.
溶质载体家族4成员4(SLC4A4)是一种编码钠/碳酸氢根共转运蛋白的膜蛋白基因,在调节pH值、碳酸氢盐分泌和体内平衡中起关键作用。然而,SLC4A4在结肠癌中的预后和免疫作用仍不清楚。
在本研究中,从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中检索SLC4A4的表达谱,并进行各种生物信息学分析。使用Sangerbox、仙桃、ESTIMATE和TIMER在线工具深入研究SLC4A4表达与免疫细胞浸润之间的关系。通过CCK8、EdU和伤口愈合试验验证SLC4A4在结肠癌细胞增殖和迁移中的作用。通过生物信息学预测和蛋白质免疫印迹分析验证SLC4A4可能影响的相关分子和途径。
SLC4A4在结肠癌组织中的表达水平显著低于正常组织,其低表达与不良预后呈正相关。TIMER和ESTIMATE显示SLC4A4广泛影响免疫细胞浸润。体外实验表明,SLC4A4抑制部分上皮-间质转化(EMT)表型。
总之,我们的研究表明SLC4A4在结肠癌组织中低表达,并且SLC4A4可能通过调节部分EMT表型和免疫细胞浸润来抑制结肠癌的进展,这可能为开发更精确和个性化的免疫抗肿瘤疗法提供新的视角。