Ornithine aminotransferase promoted the proliferation and metastasis of non-small cell lung cancer via upregulation of miR-21.

Abstract

The incidence and mortality of lung cancer ranked the first among all types of cancer in China, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for 85% of all lung cancers. Given that the survival rate of patients with advanced NSCLC is still poor nowadays, identification of novel therapeutic targets and the development of effective therapies are desired for the treatment of NSCLC in clinics. In this study, we reported the upregulation of ornithine aminotransferase (OAT) in NSCLC cells and clinical tumor samples as well as its association with the advanced TNM stage, metastasis, and poor tumor differentiation of lung cancer. Using different NSCLC cell lines, we demonstrated that OAT promoted the proliferation, invasion, and migration, inhibited the apoptosis, and altered cell cycle of NSCLC cells; besides, the involvement of OAT-miR-21-glycogen synthase kinase-3β signaling in the functional role of OAT in NSCLC was also revealed. Importantly, in the absence of OAT, the growth and metastasis of tumor lung cancer xenograft was significantly suppressed in the nude mice. Based on our findings, OAT may be a potential novel biomarker for the diagnosis and therapeutic outcome monitoring of NSCLC. Inhibition of OAT may also represent a new therapeutic strategy of NSCLC.

• Authors: Yanfeng Liu, Lei Wu, Kai Li, Fengrui Liu, Li Wang, Dongling Zhang, Jing Zhou, Xuan Ma, Shengyu Wang, Shuanying Yang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 8 Pg. 12828-12838 (08 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30549035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• MIRN21 microRNA, human
• MIRN21 microRNA, mouse
• MicroRNAs
• Ornithine-Oxo-Acid Transaminase

Topics

• Adult
• Aged
• Animals
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (drug effects, genetics)
• Middle Aged
• Ornithine-Oxo-Acid Transaminase (pharmacology)
• Up-Regulation