circGFRA1 Enhances NSCLC Progression by Sponging miR-188-3p

Background: Lung cancer continues to be one of the most dangerous tumors around the world. It is an urgency to explore the molecular mechanism of non-small cell lung cancer (NSCLC) progression for developing novel therapeutic approaches. Circular RNA (circRNA) is a novel type of non-coding RNA with a stable closed loop structure. Abnormally expressed circRNAs have been found in many kinds of cancer including NSCLC. Methods and Results: The expression of circGFRA1 and miR-188-3p was detected in NSCLC tissues by RT-qPCR and it was found that circGFRA1 was highly expressed and miR-183-3p was lowly expressed in NSCLC tissues. In NSCLC cell lines, we confirmed that circGFRA1 acted as an miR-188-3p sponge using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) analysis. Overexpression of cirGFRA1 enhanced NSCLC progression while miR-188-3p overexpression inhibited it by CCK8 and colony formation analysis. In vivo tumor xenograft model, circGFRA1 and miR-188-3p synergistically regulated the proliferation of NSCLC tumors. Mechanistic study indicated that circGFRA1 and miR-188-3p regulated the proliferation of NSCLC cells at least through PI3K/AKT signaling pathway. Conclusion: Our study elaborated a novel circGFRA-miR-188-3p-PI3K/AKT regulatory pathway, providing a potential diagnostic biomarker and therapeutic target for NSCLC.