CircPTK2 may be associated with depressive-like behaviors by influencing miR-182-5p

Background: Major depressive disorder (MDD) is a severe psychiatric disorder with uncertain causes. Recent studies have indicated correlations between circular RNAs (circRNAs) and psychiatric disorders. However, the potential role of circRNAs in MDD remains largely unknown. Methods: We investigated the expression and diagnostic significance of circRNA protein tyrosine kinase 2 (circPTK2) by recruiting 50 MDD patients and 40 healthy subjects. Additionally, chronic unpredictable mild stress (CUMS) mouse model was established in animal experiments. QRT-PCR was adopted for circPTK2 and miR-182-5p levels. To investigate the role of circPTK2 in MDD, we utilized microinjection of circPTK2 adenoassociated virus into the mouse hippocampus. Depressive-like behaviors of mice were assessed through forced swim test and open field test. Additionally, the interaction between circPTK2 and miR-182-5p was validated using a dual luciferase reporter assay. Results: Decreased expression of circPTK2 was found in peripheral blood mononuclear cells of MDD patients and in hippocampus of CUMS mice, which was useful for distinguishing MDD patients from healthy subjects. Notably, overexpression of circPTK2 was associated with depressive-like behaviors induced by CUMS. Further mechanism research demonstrated that circPTK2 functioned as the sponge for miR-182-5p, which may contribute to the beneficial effect of circPTK2. Conclusion: Collectively, our findings suggest the participation of circPTK2 and its underlying mechanism in MDD, which might provide a potential target for MDD therapy.