UPF1 regulates FOXO1 protein expression by promoting PBK transcription in non-small cell lung cancer

• Published in: Biochemical and biophysical research communications 2023-07, Vol.666, p.10-20
• Main Authors: Wang, Peng, Li, Tianjiao, Fang, Lei, Chen, Di, Qi, Huan, Gu, Chundong
• Format: Article
• Language: English
• Subjects: Carcinoma, Non-Small-Cell Lung - genetics; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; foxo1; Humans; Lung cancer; Lung Neoplasms - genetics; Nonsense Mediated mRNA Decay; pbk; RNA Helicases - genetics; RNA Helicases - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; upf1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.05.001

Up-frameshift protein 1 (UPF1) is essential for nonsense-mediated messenger RNA decay (NMD). It is best known for its cytoprotective role in degrading aberrant and specific RNAs. UPF1 is dysregulated in multiple tumors, which correlates with poor prognosis and low overall survival.However,the role of UPF1 in lung cancer remains unclear.Current study shows that UPF1 could be a potential target for oncology therapies. The results also demonstrated the potential efficiency of UPF1 in regulating the proliferation and metastasis of lung cancer. Our findings suggest that those functions can be attributed to the inhibition of the stability of FOXO1 protein. In addition, PBK participates in the regulation of FOXO1 by UPF1.This result provides a new therapeutic strategy for lung cancer patients. •UPF1 promotes the transcription of PBK.•UPF1 regulates the protein stability of FOXO1 dependent on the PBK expression.•The function of UPF1 in promoting the proliferation and metastasisi of lung cancer cells depends on FOXO1.