Solute carrier family 4 member 4 (SLC4A4) is associated with cell proliferation, migration and immune cell infiltration in colon cancer

Abstract

Abstract Background Solute Carrier Family 4 Member 4 (SLC4A4) is a membrane protein‐coding gene for a Na+/HCO3 − 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. Method 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. Results 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. Conclusions 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.

Keywords

• Colon cancer
• Pyruvate metabolism
• SLC4A4
• Partial EMT
• Immune cell infiltration