E3 ubiquitin-protein ligase 2 inhibits cell proliferation, migration, and invasion of non-small cell lung cancer through ubiquitination of Notch1

• Published in: Acta histochemica 2022-01, Vol.124 (1), p.151818-151818, Article 151818
• Main Authors: Guo, Yuening, Chi, Xiaowen, Qu, Si'ying, Sun, Yu, Liu, Jing, Zhang, Lijuan, Cao, Caihong, Wang, Yansha, Zhang, Wei
• Format: Article
• Language: English
• Subjects: Carcinoma, Non-Small-Cell Lung - metabolism; Cell Movement - genetics; Cell Proliferation - genetics; Humans; Lung Neoplasms - metabolism; MIB2; Notch1; NSCLC; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• ISSN: 0065-1281; 1618-0372
• DOI: 10.1016/j.acthis.2021.151818

This study aimed to explore the role of MIB2 in non-small cell lung cancer (NSCLC) and the underlying mechanism. Quantitative real-time PCR (QRT-PCR) and western blot were first performed to detect MIB2 expression in tumor tissues obtained from NSCLC patients (n = 30) and NSCLC cells, respectively. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and transwell assays were then used to examine the effect of MIB2 on the proliferation, migration and invasion of NSCLC cells. Western blot was further performed to examine the effect of Mind bomb 2 (MIB2), an E3 ligase on Notch1 protein and its ubiquitination. MIB2 was significantly down-regulated in NSCLC tissues and cells, both in mRNA and protein level. MIB2 also note worthily inhibited the proliferation, migration, and invasion of NSCLC cells. Furthermore, MIB2 only down-regulated Notch1 protein level, while facilitated the ubiquitination of Notch1. Additionally, Notch1 significantly relieved the repressed proliferation, migration and invasion of NSCLC cells induced by MIB2. Conclusively, MIB2 inhibited cell proliferation, migration and invasion via inducing Notch1 ubiquitination and degradation in NSCLC. •MIB2 is significantly down-regulated in NSCLC tissues and cells.•MIB2 inhibits proliferation, migration and invasion of NSCLC cells.•MIB2 induces Notch1 ubiquitination and degradation in NSCLC cells.•Notch1 relieves the repressed NSCLC cell progression induced by MIB2.