Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis.

ABSTRACT

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ_0016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ_0016760 in tissue samples and cell lines. The clinical value of circ_0016760 was also investigated. The functions of circ_0016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ_0016760 and miR-1287 and miR-1287 and GAGE1. We found that circ_0016760 was enhanced in NSCLC tissues and cells and the upregulation of circ_0016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ_0016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ_0016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ_0016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC.