Construction and dissection of the ceRNA-ceRNA network reveals critical modules in depression

The prevalence of mental health disorders such as depression is high. Depression is a multifactorial disorder and its underlying mechanisms remain unclear. Competing endogenous RNA (ceRNA) regulation has been reported to serve important roles in human disease. In the present study, ceRNA networks for depression and the corresponding normal physiological states were constructed. Further analysis of the ceRNA networks revealed that ceRNA regulation may be important for depression. Hub ceRNAs including high mobility group nucleosomal binding domain 3, peroxisome proliferator-activated receptor-γ coactivator 1β and leukemia inhibitory factor receptor-α were associated with depression. A common core ceRNA network was identified by comparison analysis. Functional analysis suggested that these ceRNAs may be implicated in depression. Differential expression analysis revealed that ceRNAs in the obtained ceRNA interaction networks were significantly enriched with significantly differentially expressed genes. A total of 8 key functional modules for depression were identified, and small target molecules were screened. ceRNA protocadherin-α subfamily C2 in module 1 and ceRNA Cyclin-dependent kinase 6 in module 3 were reported to be implicated in the occurrence and development of depressive disorders. Thus, the present analysis may provide insight into the pathogenesis of depression and improve its treatment.