The 2210408F21Rik/miR-1968-5p/Hras axis regulates synapse-related proteins in a mouse model of depressive-like behaviors through a ceRNA mechanism

Abnormal expression of long non-coding RNAs (lncRNAs) has been correlated with depressive disorders, but limited data are available on the lncRNA-microRNA (miRNA/miR)-messenger RNA (mRNA) competitive endogenous RNA (ceRNA) mechanism in depression. Herein, we address this issue based on transcriptome sequencing and in vitro experiments. Mouse hippocampus tissues were obtained from chronic unpredictable mild stress (CUMS)-induced mice to screen out differentially expressed mRNAs and lncRNAs based on the tran-scriptome sequencing. Next, the depression-related differentially expressed genes (DEGs) were obtained, fol-lowed by Gene Ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 1018 differentially expressed mRNAs, 239 differentially expressed lncRNAs, and 58 DEGs related to depression were acquired. The miRNAs targeting Harvey rat sarcoma virus oncogene (Hras) and miRNAs sponged by Hras-related lncRNA were intersected to identify the ceRNA regulatory network. In addition, the synapse-related genes related to depression were acquired by bioinformatics analysis. Hras was identified as the core gene related to depression, mainly related to neuronal excitation. We also found that 2210408F21Rik competitively bound to miR-1968-5p that targeted Hras. The effects of 2210408F21Rik/miR-1968-5p/Hras axis on neuronal excitation were verified in primary hippocampal neurons. The experimental data indicated that the downregulation of 2210408F21Rik increased the level of miR-1968-5p to diminish Hras expression, thereby affecting neuronal excitation in CUMS mice. In conclusion, the 2210408F21Rik/miR-1968-5p/Hras ceRNA network can potentially affect the expression of synapsia-related proteins and is a promising target for preventing and treating depression.