LncRNA THUMPD3-AS1 Regulates Behavioral and Synaptic Structural Abnormalities in Schizophrenia via miR-485-5p and ARHGAP8.

ABSTRACT: Schizophrenia (SCZ) is characterized by synaptic structural deficits, yet how dysregulated noncoding RNAs (ncRNAs) drive these abnormalities remains unknown. Through integrative multilayered analysis of SCZ data from whole transcriptome sequencing (blood samples), GWAS risk loci, and expression data using pipeline ceRNAxis, the THUMPD3-AS1/miR-485-5p/ARHGAP8 axis is identified as a key regulator of synaptic function. Functional validation reveals that THUMPD3-AS1 acts as a competitive endogenous RNA, sequestering miR-485-5p and thereby derepressing ARHGAP8. Despite suppressing RhoA activity, ARHGAP8 enhances ROCK2 activation through RhoB/C-mediated compensatory mechanisms. Hyperactivation of ROCK2 through this noncanonical pathway disrupted actin cytoskeletal remodeling patterns, leading t

SUBMITTER: Gong X 

PROVIDER: S-EPMC12806223 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature