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

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.