Circ_0060937 Contributes to the Development of Lung Cancer via Positively Regulating LAD1 Expression by Binding to miR-1304-5p.

Abstract

In view of the significance of circular RNA (circRNA) in multiple carcinogeneses, our study focused on circ_0060937 and investigated its function and molecular mechanism in lung cancer. Quantitative real-time PCR (qPCR) and western blot assays were applied for expression analysis of circ_0060937, miR-1304-5p, LAD1, and several marker proteins. Functional experiments, including colony formation assay, EdU assay, transwell analysis, sphere formation assay, and flow cytometry experiment, were conducted for cell behavior analysis. The putative binding relationship between circ_0060937 and miR-1304-5p was validated by dual-luciferase reporter experiment and pull-down analysis. Animal models were established to ascertain the role of circ_0060937. Upregulation of circ_0060937 was shown in lung cancer tissues and cell lines. Circ_0060937 downregulation repressed A549 and H1299 cell proliferative, migratory, invasive, and sphere formation abilities, and circ_0060937 absence also decelerated tumorigenesis in animal models. Circ_0060937 bound to miR-1304-5p to positively regulate LAD1 expression. The inhibitory effects of circ_0060937 absence on A549 and H1299 cell malignant behaviors were largely reversed by miR-1304-5p inhibition or LAD1 overexpression, hinting that circ_0060937 affected lung cancer progression via modulating the miR-1304-5p/LAD1 axis. Circ_0060937 downregulation decreased the expression of LAD1 by releasing miR-1304-5p to effectively repress lung cancer cell growth and in vivo tumorigenesis.