circMET promotes NSCLC cell proliferation, metastasis, and immune evasion by regulating the miR-145-5p/CXCL3 axis

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 lar...

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Published in:Aging (Albany, NY.) NY.), 2020-07, Vol.12 (13), p.13038-13058
Main Authors: Pei, Xu, Chen, Shi-Wei, Long, Xiang, Zhu, Shu-Qiang, Qiu, Bai-Quan, Lin, Kun, Lu, Feng, Xu, Jian-Jun, Zhang, Peng-Fei, Wu, Yong-Bing
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Cell Proliferation - genetics
Chemokines, CXC - genetics
Chemokines, CXC - metabolism
Female
Humans
Immune Evasion - genetics
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Proto-Oncogene Proteins c-met - genetics
Proto-Oncogene Proteins c-met - metabolism
Research Paper
RNA, Circular - genetics
RNA, Circular - metabolism
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.103392