Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis

Lu，Yongbin1; Su，Fei2; Cheng，Zhiyuan3; Yang，Jingli4; Dai，Huanyu2; Yang，Jingru2; Zhang，Tao2; Bai，Yana4

2023-11-01

10.1016/j.lfs.2023.122111

Life Sciences   影响因子和分区

0024-3205

1879-0631

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 (NiCl) exposure promotes invasion and metastasis through IL-6/STAT3 both in vitro and vivo. Mechanistically, we found that NiCl 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 NiCl 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 NiCl in lung cancer progression, indicating that STAT3 and TRIM31 may be promising targets for the treatment of lung cancer.

Lung cancer NiCl2 STAT3 TP53 TRIM31 Ubiquitination

SCI

英语

其他

National Natural Science Foundation of China["82303524","82260518"] ; Gansu Provincial Natural Science Foundation["21JR7RA384","22JR5RA918","21JR11RA079","23JRRA1497"] ; Gansu Provincial Department of Education Project[2022B-003] ; Lanzhou Science and Technology Plan Project[2020-ZD-75] ; In-hospital Fund of the First Hospital of Lanzhou University[ldyyyn2022-65]

Research & Experimental Medicine ; Pharmacology & Pharmacy

Medicine, Research & Experimental ; Pharmacology & Pharmacy

WOS:001105932700001

PERGAMON-ELSEVIER SCIENCE LTD

BIOLOGY & BIOCHEMISTRY

2-s2.0-85171836810

Scopus

1.College of Earth and Environmental Sciences,School of Basci Medical Sciences,The First Hospital of Lanzhou University,Lanzhou University,Lanzhou,Gansu,China
2.Department of Oncology,The First Hospital of Lanzhou University,Lanzhou,Gansu,China
3.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,China
4.College of Earth and Environmental Sciences,Department of Epidemiology and Statistics,Lanzhou university,Lanzhou,Gansu,China

Lu，Yongbin,Su，Fei,Cheng，Zhiyuan,et al. Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis[J]. Life Sciences,2023,332.

Lu，Yongbin.,Su，Fei.,Cheng，Zhiyuan.,Yang，Jingli.,Dai，Huanyu.,...&Bai，Yana.(2023).Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis.Life Sciences,332.

Lu，Yongbin,et al."Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis".Life Sciences 332(2023).