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Supplementary table 9 from Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A

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posted on 2023-03-31, 20:22 authored by Shuye Lin, Xiaoyue Wang, Yuanming Pan, Rongmeng Tian, Bonan Lin, Guosheng Jiang, Keqiang Chen, Yuqi He, Lulu Zhang, Wanli Zhai, Peng Jin, Lang Yang, Guoqiang Li, Yun Wu, Jiang Hu, Wanghua Gong, Zhijie Chang, Jian-qiu Sheng, Youyong Lu, Ji Ming Wang, Jiaqiang Huang

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Funding

National Science Foundation of China

National Cancer Institute, National Institutes of Health

Army Special Care

Beijing Municipal Natural Science Foundation

China Postdoctoral Science Foundation

Inner Mongolia Autonomous Region Natural Science Foundation

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ARTICLE ABSTRACT

Metallothionein 2A (MT2A) suppresses the progression of human gastric cancer potentially through an “MT2A–NF-κB pathway” with unclear mechanisms. This study explored the role of a transcription factor, myeloid zinc-finger 1 (MZF1), in MT2A-NF-κB pathway and its clinical significance in gastric cancer. MZF1 expression and function in gastric cancer were investigated in vitro and in vivo. The relationship between MZF1 and MT2A was determined by gain-of-function and loss-of-function assays in gastric cancer cells and an immortalized gastric cell line GES-1. The prognostic value of MZF1 expression in association with MT2A was evaluated using IHC in two cohorts. MZF1 was epigenetically silenced in human gastric cancer cell lines and primary tumors. Overexpression of MZF1 in gastric cancer cells suppressed cell proliferation and migration, as well as the growth of xenograft tumors in nude mice. Knocking-down of MZF1 transformed GES-1 cells into a malignant phenotype characterized by increased cell growth and migration. Mechanistically, MZF1 was upregulated in both GC and GES-1 cells by MT2A ectopically expressed or induced upon treatment with a garlic-derived compound, diallyl trisulfide (DATS). MZF1 associated with MT2A was colocalized in the nuclei of GES-1 cells to target the promoter of NF-κB inhibitor alpha (NFKBIA). Clinically, MT2A and MZF1 were progressively downregulated in clinical specimens undergoing gastric malignant transformation. Downregulation of MT2A and MZF1 was significantly correlated with poorer patient prognosis. MT2A exerts its anti-gastric cancer effects by complexing with MZF1 to target NFKBIA. MT2A/MZF1 may serve as a valuable prognostic marker and a novel therapeutic target for human gastric cancer.

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