circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway.

This study aims to explore the role and mechanism of circ-IARS in non-small-cell lung cancer (NSCLC) progression. Expression of circ-IARS, microRNA (miR)-1252-5p, and hepatoma-derived growth factor (HDGF) was measured by real-time quantitative PCR and western blotting. The interactions among circ-IARS, miR-1252-5p, and HDGF were determined by dual-luciferase reporter assay and RNA immunoprecipitation. Cell behaviors were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, scratch wound assay, and transwell assay, and validated in xenograft model. Exosomes were isolated using commercial kit, and the expression and functions of exosomal circ-IARS (exo-circ-IARS) were analyzed as described above. Results showed that the expression of circ-IARS was upregulated in NSCLC cells, NSCLC tissues, and serum exosomes from NSCLC patients. circ-IARS exhaustion antagonized cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in NSCLC. Molecularly, circ-IARS could sponge miR-1252-5p to modulate the expression of the downstream gene HDGF. In addition, miR-1252-5p downregulation attenuated circ-IARS exhaustion-mediated effects in H1299 and A549 cells. MiR-1252-5p mimic-induced effects were relieved by increasing HDGF expression in H1299 and A549 cells. Exo-circ-IARS promoted H460 cell proliferation, migration, and invasion and inhibited cell apoptosis. Silencing circ-IARS retarded tumor growth of NSCLC cells . Thus, circ-IARS, secreted by exosomes, was a novel oncogene in NSCLC and regulated the malignant development of NSCLC cells via circ-IARS/miR-1252-5p/HDGF competing endogenous RNA regulatory axis.