镍化合物作为重要的工业产品，广泛应用于工业和日常生活中。长期接触镍化合物与肺癌发病率上升和预后不良有关。然而，镍化合物引起肺癌细胞恶性表型的分子机制尚不清楚。本研究证实了镍氯化物（NiCl2）暴露通过IL-6/STAT3在体内外促进侵袭和转移。机制上，我们发现NiCl2介导了通过SATAT3磷酸化调控E3泛素连接酶TRIM31的转录调控，并促进了其上调。TRIM31的过表达是肺癌患者的独立风险因素，并促进了肺癌细胞的侵袭和转移。此外，E3泛素连接酶TRIM31通过其RING区域与底物TP53蛋白结合，加速了TP53蛋白的泛素化和降解。功能恢复实验表明，NiCl2暴露通过STAT3/TRIM31轴促进了肺癌的侵袭和转移能力，以及通过泛素化介导的TP53蛋白降解。这些发现揭示了NiCl2在肺癌进展中的作用和机制，表明STAT3和TRIM31可能是肺癌治疗的有希望的靶点。版权所有 © 2023. Elsevier Inc.发表。

Nickel compounds are widely used in industries and daily life as important industrial products. Long-term exposure to nickel compounds has been associated with increased incidence and poor prognosis of lung cancer. However, the molecular mechanism by which exposure to nickel compounds induces the malignant phenotype of lung cancer cells remains unclear. In this study, we confirmed that nickel chloride (NiCl2) exposure promotes invasion and metastasis through IL-6/STAT3 both in vitro and vivo. Mechanistically, we found that NiCl2 mediated the transcriptional regulation of E3 ubiquitin ligase TRIM31 by SATAT3 phosphorylation, and promoted its up-regulation. Overexpression TRIM31 is an independent risk factor for lung cancer patients, and it promotes the invasion and metastasis of lung cancer cells. In addition, E3 ubiquitination ligase TRIM31 binds to its substrate TP53 protein in the RING region and accelerates TP53 protein ubiquitination and degradation. Functional recovery experiments showed that NiCl2 exposure promotes the invasion and metastasis ability of lung cancer and ubiquitination-mediated degradation of TP53 protein through the STAT3/TRIM31 axis. These findings reveal the role and mechanism of NiCl2 in lung cancer progression, indicating that STAT3 and TRIM31 may be promising targets for the treatment of lung cancer.Copyright © 2023. Published by Elsevier Inc.