Identification of the tumor-suppressive function of circular RNA FOXO3 in non-small cell lung cancer through sponging miR-155

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that have been demonstrated to be potential regulators in the development and progression of various types of human cancer. However, little is known about their roles in cancer initiation and progression, particular in non-small cell lung cancer (NSCLC). In the present study, the expression level of circRNA-forkhead box O3 class (FOXO3) in NSCLC specimens was determined and its functional role was investigated in NSCLC cells. By performing Taq-man based RT-qPCR, it was identified that circRNA-FOXO3 was downregulated in NSCLC tissues and cell lines. Receiver operating curve analysis indicated that circRNA-FOXO3 had a relatively higher diagnostic accuracy. The functional relevance was further examined by biological assays. circRNA-FOXO3 significantly promoted the ability of cell proliferation, migration and invasion of NSCLC cells. The linear isomer of circRNA-FOXO3, FOXO3 gene, was identified as a downstream target. RNA immunoprecipitation indicated that circRNA-FOXO3 sequestering miR-155, which further promoted linear FOXO3 expression. In addition, gain and loss functional assays indicated that circRNA-FOXO3 served an anti-oncogenic role through sequestering miR-155 and enhancing FOXO3 expression. These results suggest that circRNA-FOXO3 is a tumor-suppressor in NSCLC and may serve as a promising therapeutic target. Therefore, restoration of circRNA-FOXO3 expression could be a future approach to develop a novel treatment strategy.