Double homeobox a pseudogene 8/miR-223-3p/PFN2 modulates radiosensitivity in lung cancer

BackgroundLong noncoding RNA double homeobox A pseudogene 8 (DUXAP8) was revealed to facilitate lung cancer progression in vitro, but the impacts of DUXAP8 on modulating radiosensitivity have not been examined.ObjectiveThis study aimed to explore the effect and underlying mechanisms of DUXAP8 in regulating radiosensitivity in lung cancer.MethodsBioinformatic tools were used to evaluate expression level of DUXAP8 and its associations with overall survival of patients with lung cancer. RT-qPCR was applied to examine the level of DUXAP8, miR-223-3p and profilin 2 (PFN2) RNA expression. Viabilities and apoptosis rates were measured. The interactions of miR-223-3p and DUXAP8 or PFN2 were confirmed using dual-luciferase reporter test and RNA immunoprecipitation (RIP). Immunohistochemistry (IHC) was used to examine Ki67 in animal models.ResultsDUXAP8 was elevated in lung cancer tissue samples and decreased overall survival of patients. Moreover, DUXAP8 was elevated in lung cancer cells, while irradiation treatment suppressed DUXAP8 in A549 cells. The knockdown of DUXAP8 inhibited cell viabilities but facilitated cell apoptosis. MiR-223-3p was sponged by DUXAP8, while PFN2 was targeted by miR-223-3p but positively modulated by DUXAP8. PFN2 upregulation reversed the effect of miR-223-3p mimics. In animal models, knockdown of DUXAP8 inhibited tumor growth and enhanced radiosensitivity.ConclusionDUXAP8/miR-223-3p/PFN2 axis modulated radiosensitivity in lung cancer.