Circ_0016760 Serves as a Cancer Promoter in Non-small Cell Lung Cancer Through miR-876-3p/NOVA2 Axis

Non-small cell lung cancer (NSCLC) is a serious threaten to human health globally. Circular RNAs (circRNAs) were testified to alter the progression of NSCLC. This work intended to investigate the functional role of circ_0016760 in NSCLC development and the potential mechanism. Expression of circ_0016760, microRNA (miR)-876-3p and NOVA alternative splicing regulator 2 (NOVA2) was determined via quantitative reverse transcription-PCT (qRT-PCR) or western blotting. Cell viability, clonogenicity and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry, respectively. Transwell assay was performed to examine cell migration and invasion. Western blotting was also conducted to detect the levels of epithelial-to-mesenchymal transition (EMT)-related proteins. Role of circ_0016760 in vivo was evaluated via xenograft model assay. Moreover, the interaction between miR-876-3p and circ_0016760 or NOVA2 was verified by dual-luciferase reporter assay or RNA Immunoprecipitation (RIP) assay. Circ_0016760 and NOVA2 were upregulated, while miR-876-3p expression was decreased in NSCLC tissues and cells. Circ_0016760 depletion suppressed NSCLC cell proliferation and metastasis in vitro, as well as hampered tumor growth in vivo. Circ_0016760 acted as a sponge of miR-876-3p, and miR-876-3p could target NOVA2. Circ_0016760 might play vital roles in NSCLC by regulating miR-876-3p/NOVA2 axis. Circ_0016760 could promote the malignant development of NSCLC through miR-876-3p/NOVA2 axis, at least in part. Graphical Abstract: [Figure not available: see fulltext.]