Xing Yamin, Li Guangyuan, Li Ganggang, Xu Jixuan, Zhang Ting, Li Mengxue, Gao Chunxiao, Fu Miaoran, Zheng Pengyuan, Chu Xiufeng
Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Sci Rep. 2025 Mar 18;15(1):9339. doi: 10.1038/s41598-025-91319-y.
Metallothioneins (MTs) are a class of cysteine-rich proteins that actively participate in the cellular defense against free radicals. However, owing to the high heterogeneity among different MTs, comprehensive investigations are needed to determine the biological activities and distribution patterns of each MT in different tissues. In the present study, ectopic expression of MT1H significantly inhibited the proliferation of gastric cancer cells. Mechanistically, MT1H was transported into the nucleus and regulated the expression of key genes involved in nutrient transportation and homeostasis, such as SLC6A19, TTC39B, and ADM2, and thereby activating the p53 and autophagy pathways. Additionally, survival analysis of data from the TCGA and other databases revealed that gastric cancer patients with high expression of MT1H had longer survival. Furthermore, MT1H was undetectable in most gastric cell lines, but its expression was increased upon treatment with dexamethasone (Dexa) and the metal ion zinc. Therefore, MT1H emerges as a valuable tumor suppressor, a biomarker for the prognosis, and a promising therapeutic target in gastric cancer patients.
金属硫蛋白（MTs）是一类富含半胱氨酸的蛋白质，可积极参与细胞对自由基的防御。然而，由于不同MT之间存在高度异质性，需要进行全面研究以确定每种MT在不同组织中的生物学活性和分布模式。在本研究中，MT1H的异位表达显著抑制了胃癌细胞的增殖。机制上，MT1H被转运到细胞核中，并调节参与营养物质运输和体内平衡的关键基因（如SLC6A19、TTC39B和ADM2）的表达，从而激活p53和自噬途径。此外，对来自TCGA和其他数据库的数据进行的生存分析表明，MT1H高表达的胃癌患者生存期更长。此外，在大多数胃癌细胞系中未检测到MT1H，但其表达在用地塞米松（Dexa）和金属离子锌处理后增加。因此，MT1H有望成为一种有价值的肿瘤抑制因子、预后生物标志物以及胃癌患者有前景的治疗靶点。
