Zhang Xi, Liu Yan, Peng Bai-Zhao, Zhou Xing-Hong, You Yan-Ting, Yang Ying, Ji Shuai, Zhong Tian-Yu, Chen Xiao-Hu, Liu Yan-Yan, Zhao Xiao-Shan
Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Front Immunol. 2025 Apr 8;16:1519815. doi: 10.3389/fimmu.2025.1519815. eCollection 2025.
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) and . 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.
锌指同源盒3（TSHZ3）是一种与某些癌症进展相关的转录因子。然而，其在肺腺癌（LUAD）中的表达和功能仍不清楚。因此，我们旨在研究TSHZ3在LUAD患者中的表达，并评估其预后意义。首先，我们通过生物信息学分析探索了预后数据并预测了TSHZ3在肺癌中的功能。然后，我们使用细胞和动物实验验证了这些功能。我们的结果表明，与正常肺组织相比，LUAD中TSHZ3的表达显著降低。TSHZ3高表达与LUAD患者更好的总生存期呈正相关。基因本体（GO）和通路分析表明，TSHZ3参与免疫反应和各种癌症相关过程。免疫浸润分析揭示了TSHZ3与免疫细胞浸润之间的相关性，特别是巨噬细胞，以及多种免疫刺激因子、趋化因子和受体的表达。我们的实验结果表明，TSHZ3过表达抑制细胞迁移、侵袭和上皮-间质转化（EMT），并且过表达TSHZ3的LUAD细胞由于CD86+巨噬细胞的募集而更容易发生凋亡。此外，过表达TSHZ3的LUAD细胞中CCL2的表达显著更高，而共培养的巨噬细胞中CCR2的表达也显著上调。这些发现表明，TSHZ3是一种重要的肿瘤抑制因子，它通过抑制EMT和转移，同时通过CCL2/CCR2诱导M1巨噬细胞趋化来诱导凋亡。
