Integrated Expression and Bioinformatic Analysis of AKT-Associated lncRNAs Suggests UCA1 as a Candidate Biomarker for Bipolar Disorder.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent disturbances in mood and behavior. Given the reported involvement of the AKT signaling pathway in BD, we investigated the expression of three AKT-associated long non-coding RNAs (LINC-ROR, MALAT1, and UCA1) in peripheral blood samples from patients with BD and healthy controls. Furthermore, we performed exploratory bioinformatic analyses to identify potential lncRNA-miRNA and lncRNA-RNA-binding protein interaction networks. In the present study, we evaluated the expression profiles of three AKT signaling pathway-associated lncRNAs, namely LINC-ROR, MALAT1, and UCA1, in peripheral blood samples from patients with BD. We compared these findings with those from healthy control subjects. Additionally, an in silico analysis was performed to investigate potential microRNA (miRNA) binding sites within these lncRNAs and to assess their interactions with RNA-binding proteins (RBPs), thereby providing further insight into their potential regulatory roles in BD pathogenesis. MALAT1 and UCA1 expression levels were significantly higher in patients with BD than in healthy controls. Although LINC-ROR expression showed a trend toward downregulation, the difference did not remain statistically significant after Bonferroni correction for multiple comparisons. Among the investigated lncRNAs, UCA1 exhibited the strongest discriminatory performance in differentiating individuals with BD from control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.75 (P < 0.0001, 95% CI: 65%-84%). Previous evidence demonstrating the involvement of the AKT signaling pathway in the pathogenesis of BD further supports the hypothesis that dysregulation of pathway-associated lncRNAs contributes to the disorder. These findings support the involvement of AKT-associated lncRNAs in BD pathophysiology and suggest that UCA1 may represent a candidate biomarker requiring further validation in larger independent cohorts.