Research Paper Volume 12, Issue 13 pp 13038—13058
circMET promotes NSCLC cell proliferation, metastasis, and immune evasion by regulating the miR-145-5p/CXCL3 axis
- 1 Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- 2 Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
Received: December 11, 2019 Accepted: May 1, 2020 Published: July 2, 2020
https://doi.org/10.18632/aging.103392How to Cite
Copyright © 2020 Pei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In recent years, circular RNAs (circRNAs) have been increasingly reported to play a crucial role in the proliferation, migration, and invasion of non-small-cell lung cancer (NSCLC) cells. However, the circRNA MET (circMET) oncogenic mechanism that drives NSCLC development and progression remains largely unknown. In this study, the present results demonstrated that circMET expression was significantly higher in NSCLC tissues than in peritumoral tissues using quantitative real-time polymerase chain reaction. Notably, NSCLC patients with a large tumor diameter, poor differentiation and lymphatic metastasis had high RNA levels of circMET. Moreover, high circMET expression served as an independent risk factor for short overall survival (OS) and progression-free survival (PFS) in NSCLC patients. Next, we validated that circMET overexpression can enhance NSCLC cell proliferation, metastasis, and immune evasion in vitro. Mechanistically, our study uncovers that circMET acts as a miR-145-5p sponge to upregulate CXCL3 expression. Collectively, circMET regulates the miR-145-5p/CXCL3 axis and serves as a novel, promising diagnostic and prognostic biomarker in patients with NSCLC.
Abbreviations
NSCLC: non-small-cell lung cancer; circRNA: circular RNA; MET: mesenchymal epithelial transition factor receptor; CXCL3: chemokine (C-X-C motif) ligand 3; CCK-8: Cell Counting Kit-8; IHC: Immunohistochemistry; RT-qPCR: Quantitative real-time polymerase chain reaction; FISH: Fluorescence in situ hybridization; TMAs: Tissue microarrays.