Circular non‐coding RNA circ_0072088 serves as a ceRNA, targeting the miR‐1225‐5p/WT1 axis to regulate non‐small cell lung cancer cell malignant behavior

Abstract

Abstract Background Circular RNA (circRNA) circ_0072088 has been reported to be associated with NSCLC cell growth, migration, and invasion. However, the role and mechanism of circ_0072088 on NSCLC development have not yet been determined. Methods Circ_0072088, microRNA‐1225 (miR‐1225‐5p), and Wilms' tumor (WT1) suppressor gene level was detected by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Migration, invasion, and apoptosis were detected using transwell and flow cytometry assays. Matrix metallopeptidase 9 (MMP9), hexokinase 2 (HK2), and WT1 were examined using western blot assay. The biological role of circ_0072088 on NSCLC tumor growth was examined by the xenograft tumor model in vivo. Circular RNA Interactome and TargetScan were used to predict the binding between miR‐1225‐5p and circ_0072088 or WT1, followed by confirmation using a dual‐luciferase reporter. Results Circ_0072088 and WT1 were highly expressed in NSCLC tissues and cells, and miR‐1225‐5p was decreased. Knockdown of circ_0072088 might repress migration, invasion, and glycolysis, and facilitate apoptosis of NSCLC cells in vitro. Circ_0072088 silencing also blocked NSCLC tumor growth in vivo. Mechanistically, circ_0072088 acted as a sponge of miR‐1225‐5p to regulate WT1 expression. Conclusion Circ_0072088 knockdown could inhibit cell growth, migration, invasion, and glycolysis partially by regulating the miR‐1225‐5p/WT1 axis, thus providing a promising therapeutic target for NSCLC treatment.

Keywords

• Circ_0072088
• miR‐1225‐5p
• non‐small cell lung cancer
• WT1