The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma

Teashirt zinc finger homeobox 3 (TSHZ3) is a transcription factor implicated in the progression of certain cancers. However, its expression and function in lung adenocarcinoma (LUAD) remain unclear. Therefore, we aimed to investigate TSHZ3 expression and assess its prognostic significance in LUAD patients. First, we explored prognostic data and predicted the function of TSHZ3 in lung cancer through bioinformatics analysis. We then validated the functions using cellular and animal experiments. Our results indicated that TSHZ3 expression was significantly lower in LUAD compared to normal lung tissues. High TSHZ3 expression was positively associated with better overall survival in LUAD patients. GO and pathway analyses suggested that TSHZ3 is involved in immune responses and various cancer-related processes. Immune infiltration analysis revealed correlations between TSHZ3 and immune cell infiltration, particularly macrophages, as well as the expression of numerous immune stimulators, chemokines, and receptors. Our experiment results suggest that TSHZ3 overexpression inhibits cell migration, invasion, and epithelial-mesenchymal transition (EMT) <i>in vivo</i> and <i>in vitro</i>. LUAD cells overexpressing TSHZ3 were more prone to apoptosis due to the recruitment of CD86+ macrophages. In addition, CCL2 expression was significantly higher in LUAD cells overexpressing TSHZ3, while CCR2 expression was also significantly upregulated in co-cultured macrophages. These findings suggest that TSHZ3 is an important tumor suppressor by inhibiting EMT and metastasis while inducing apoptosis through M1 macrophage chemotaxis via the CCL2/CCR2.