MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy
Abstract 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...
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| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-91319-y |
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| author | Yamin Xing Guangyuan Li Ganggang Li Jixuan Xu Ting Zhang Mengxue Li Chunxiao Gao Miaoran Fu Pengyuan Zheng Xiufeng Chu |
| author_facet | Yamin Xing Guangyuan Li Ganggang Li Jixuan Xu Ting Zhang Mengxue Li Chunxiao Gao Miaoran Fu Pengyuan Zheng Xiufeng Chu |
| author_sort | Yamin Xing |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b1dd7114f04644f78da897c537a60af8 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b1dd7114f04644f78da897c537a60af82025-08-20T03:41:49ZengNature PortfolioScientific Reports2045-23222025-03-0115111710.1038/s41598-025-91319-yMT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagyYamin Xing0Guangyuan Li1Ganggang Li2Jixuan Xu3Ting Zhang4Mengxue Li5Chunxiao Gao6Miaoran Fu7Pengyuan Zheng8Xiufeng Chu9Marshall B. J. Medical Research Center, Zhengzhou UniversityMarshall B. J. Medical Research Center, Zhengzhou UniversityDepartment of Oncology, The Fifth Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal & Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The Fifth Affiliated Hospital of Zhengzhou UniversityMarshall B. J. Medical Research Center, Zhengzhou UniversityMarshall B. J. Medical Research Center, Zhengzhou UniversityDepartment of Neurology, The Fifth Affiliated Hospital of Zhengzhou UniversityMarshall B. J. Medical Research Center, Zhengzhou UniversityMarshall B. J. Medical Research Center, Zhengzhou UniversityAbstract 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.https://doi.org/10.1038/s41598-025-91319-yMetallothioneinGastric cancerp53Autophagy |
| spellingShingle | Yamin Xing Guangyuan Li Ganggang Li Jixuan Xu Ting Zhang Mengxue Li Chunxiao Gao Miaoran Fu Pengyuan Zheng Xiufeng Chu MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy Scientific Reports Metallothionein Gastric cancer p53 Autophagy |
| title | MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy |
| title_full | MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy |
| title_fullStr | MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy |
| title_full_unstemmed | MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy |
| title_short | MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy |
| title_sort | mt1h inhibits the growth of gastric cancer by regulating slc6a19 ttc39b adm2 and activating p53 dependent autophagy |
| topic | Metallothionein Gastric cancer p53 Autophagy |
| url | https://doi.org/10.1038/s41598-025-91319-y |
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