CircFBXW8 Acts an Oncogenic Role in the Malignant Progression of Non-small Cell Lung Carcinoma by miR-370-3p-Dependent Regulation of TRIM44.

Non-small cell lung carcinoma (NSCLC) is an aggressive malignant tumor. Growing evidences have revealed that circular RNA (circRNA) is involved in NSCLC progression. This study aims to investigate the role of circular RNA F-box and WD repeat domain containing 8 (circFBXW8) in NSCLC progression and the underlying mechanism. The expression of circFBXW8, microRNA-370-3p (miR-370-3p) and tripartite motif containing 44 (TRIM44) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blot analysis or immunohistochemistry assay. Additionally, cell viability, colony-forming ability, proliferation and apoptosis were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, cell colony formation, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis assays, respectively. Cell migratory and invasive abilities were examined by wound-healing and transwell assays. The regulatory relationship between miR-370-3p and circFBXW8 or TRIM44 was identified by dual-luciferase reporter and RNA pull-down assays. Furthermore, xenograft experiment was employed to explain the effect of circFBXW8 silencing on tumor formation. CircFBXW8 and TRIM44 expression were upregulated, while miR-370-3p was downregulated in NSCLC tissues, cells and the exosomes from NSCLC cells compared with respective controls. CircFBXW8 depletion repressed NSCLC cell proliferation, migration and invasion, but promoted cell apoptosis. CircFBXW8 acted as a sponge of miR-370-3p and regulated NSCLC cell malignancy by binding to miR-370-3p. Additionally, miR-370-3p repressed NSCLC cell processes by regulating TRIM44. CircFBXW8 knockdown inhibited tumor formation in vivo. Further, circFBXW8 secretion was mediated by exosomes. CircFBXW8 modulated NSCLC progression by increasing TRIM44 expression through sponging miR-370-3p, which provided a new direction for studying the therapy of NSCLC.