Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia


Sabaie H., Gharesouran J., Asadi M. R. , Farhang S., Ahangar N. K. , Brand S., ...More

METABOLIC BRAIN DISEASE, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1007/s11011-022-00918-5
  • Journal Name: METABOLIC BRAIN DISEASE
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, EMBASE, MEDLINE
  • Keywords: 22q11, 2 deletion syndrome, CKAMP59, miR-185, Schizophrenia, SHISA7, LOW-COPY REPEATS, SYNAPTIC PLASTICITY, PREFRONTAL CORTEX, EXPRESSION, RECEPTORS, MEDIATE, HUMANS, GENES, CELLS

Abstract

Schizophrenia (SCZ) is known as a complicated mental disease with an unknown etiology. The microdeletion of 22q11.2 is the most potent genetic risk factor. Researchers are still trying to find which genes in the deletion region are linked to SCZ. MIR185, encoding microRNA (miR)-185, is present in the minimal 1.5 megabase deletion. Nonetheless, the miR-185 expression profile and its corresponding target genes in animal models and patients with 22q11.2 deletion syndrome (22q11.2DS) imply that more study is required about miR-185 and its corresponding downstream pathways within idiopathic SCZ. The expression of hsa-miR-185-5p and its corresponding target gene, shisa family member 7 (SHISA7), sometimes called CKAMP59, were evaluated in the peripheral blood (PB) samples of Iranian Azeri patients with idiopathic SCZ and healthy subjects, matched by gender and age as control groups by quantitative polymerase chain reaction (qPCR). Fifty SCZ patients (male/female: 22/28, age (mean +/- standard deviation (SD)): 35.9 +/- 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean +/- SD): 34.7 +/- 5.4) were enrolled. The expression of hsa-miR-185-5p in the PB samples from subjects with idiopathic SCZ was substantially lower than in that of control groups (posterior beta = -0.985, adjusted P-value < 0.0001). There was also a difference within the expression profile between female and male subgroups (posterior beta = -0.86, adjusted P-value = 0.046 and posterior beta = -1.015, adjusted P-value = 0.004, in turn). Nevertheless, no significant difference was present in the expression level of CKAMP59 between PB samples from patients and control groups (adjusted P-value > 0.999). The analysis of the receiver operating characteristic (ROC) curve suggested that hsa-miR-185-5p may correctly distinguish subjects with idiopathic SCZ from healthy people (the area under curve (AUC) value: 0.722). Furthermore, there was a strong positive correlation between the expression pattern of the abovementioned genes in patients with SCZ and healthy subjects (r = 0.870, P < 0.001 and r = 0.812, P < 0.001, respectively), indicating that this miR works as an enhancer. More research is needed to determine if the hsa-miR-185-5p has an enhancer activity. In summary, this is the first research to highlight the expression of the miR-185 and CKAMP59 genes in the PB from subjects with idiopathic SCZ. Our findings suggest that gene expression alterations mediated by miR-185 may play a role in the pathogenesis of idiopathic and 22q11.2DS SCZ. It is worth noting that, despite a substantial and clear relationship between CKAMP59 and hsa-miR-185-5p, indicating an interactive network, their involvement in the development of SCZ should be reconsidered based on the whole blood sample since the changed expression level of CKAMP59 was not significant. Further research with greater sample sizes and particular leukocyte subsets can greatly make these results stronger.