肿瘤坏死因子-α诱导蛋白 3 在胃癌恶性转化中的潜在作用。

The potential role of TNFAIP3 in malignant transformation of gastric carcinoma.

机构信息

Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 148 Baojian Road, Nangang District, Harbin, 150081, People's Republic of China.

Department of Internal Medicine, Harbin Medical University Cancer Hospital, 6 Baojian Road, Nangang District, Harbin, 150040, People's Republic of China.

出版信息

Pathol Res Pract. 2019 Aug;215(8):152471. doi: 10.1016/j.prp.2019.152471. Epub 2019 May 24.

DOI:10.1016/j.prp.2019.152471

PMID:31153693

Abstract

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a deubiquitinating enzyme, plays an essential regulatory role in inflammation, immune responses and tumorigenesis. Our present study indicates that TNFAIP3 is required for the ubiquitination degradation of epithelial-mesenchymal transition (EMT) related transcription factors Snail and ZEB1, which further altered the expression of EMT-related marker proteins and eventually contributing to the malignant phenotype and poorer prognosis of gastric carcinoma. Depletion of TNFAIP3 attenuated the capacity of proliferation, migration and invasion of gastric cancer cells in vitro. Taken together, these findings propose a pathway linking the TNFAIP3 to the EMT-mediated metastatic process in gastric cancer, which provides a viable strategy regarding the interventions and prognostic analysis of gastric carcinoma in clinical practice.

摘要

肿瘤坏死因子α诱导蛋白 3（TNFAIP3）是一种去泛素化酶，在炎症、免疫反应和肿瘤发生中发挥重要的调节作用。本研究表明，TNFAIP3 对于上皮-间充质转化（EMT）相关转录因子 Snail 和 ZEB1 的泛素化降解是必需的，这进一步改变了 EMT 相关标记蛋白的表达，最终导致胃癌的恶性表型和较差的预后。TNFAIP3 的耗竭减弱了胃癌细胞体外增殖、迁移和侵袭的能力。总之，这些发现提出了一条通路，将 TNFAIP3 与胃癌中的 EMT 介导的转移过程联系起来，这为临床实践中胃癌的干预和预后分析提供了可行的策略。