Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.
Keywords: CircZMYM4; Lung adenocarcinoma; Metastasis; ODAM; ceRNA; miR-587.
Copyright © 2021. Published by Elsevier Inc.