Background Circular RNA (circRNA) plays a crucial role in non‐small cell lung cancer (NSCLC) progression. However, the role of circCCDC134 in NSCLC is still largely unknown. Methods Quantitative real‐time PCR was utilized for measuring circCCDC134, microRNA (miR)‐625‐5p and nuclear factor of activated T cell 5 (NFAT5) expression. Cell functions were evaluated by colony formation, EdU, transwell, and wound healing assays and flow cytometry. Glucose consumption, lactate production, and ATP level were determined to analyze cell glycolysis. Western blot analysis was used to detect protein expression. Animal experiments were performed to assess the effect of circCCDC134 on NSCLC tumor growth. RNA interaction was evaluated by dual‐luciferase reporter assay and RIP assay. Exosomes were isolated from the serum of NSCLC patients and healthy normal controls. Results Highly expressed circCCDC134 was found in NSCLC tissues and cells, as well as in the serum exosomes of NSCLC patients. Downregulated circCCDC134 restrained NSCLC cell growth, metastasis and glycolysis. CircCCDC134 sponged miR‐625‐5p to regulate NFAT5. MiR‐625‐5p inhibitor abolished the regulation of circCCDC134 knockdown on NSCLC progression, and NFAT5 overexpression eliminated the effects of miR‐625‐5p on NSCLC cell behaviors. CircCCDC134 knockdown also inhibited NSCLC tumor growth. Conclusion Our study revealed that circCCDC134 was involved in regulating NSCLC progression through the miR‐625‐5p/NFAT5 pathway, confirming that circCCDC134 might function as the diagnostic and therapeutic target for NSCLC.
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