Identification of key long non-coding RNA-associated competing endogenous RNA axes in Brodmann Area 10 brain region of schizophrenia patients

Abstract

Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs (PEG3-AS1, MIR570HG), seven key miRNAs (hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-29b-3p), and eight key mRNAs (EGR1, ETV1, DUSP6, PLOD2, CD93, SERPINB9, ANGPTL4, TGFB2). Furthermore, DEmRNAs were found to be enriched in the “AGE-RAGE signaling pathway in diabetic complications”, “Amoebiasis”, “Transcriptional misregulation in cancer”, “Human T-cell leukemia virus 1 infection”, and “MAPK signaling pathway”. This study offers research targets for examining significant molecular pathways connected to the pathogenesis of SCZ, even though the function of these ceRNA axes still needs to be investigated.

Alteration of microRNA expression in lymphocytes in patients with first-episode schizophrenia

“…MiR-107 has been found signi cantly upregulated in the prefrontal cortex of patients with SCZ (31). A previous study found that miR-181a was upregulated in brain post-mortem tissues of schizophrenia (47). Schizophrenia patients had considerably higher serum levels of miR-223.…”

Disclosing common biological signatures and predicting new therapeutic targets in schizophrenia and obsessive–compulsive disorder by integrated bioinformatics analysis

“…Interestingly, the level of hsa-miR-22-3p also significantly increased in patients with OCD compared to healthy subjects [ 95 ]. A bioinformatics study on microarray dataset from brain post-mortem samples of SCZ patients identified hsa-miR-26a-5p as a differentially expressed miRNA compared to control samples [ 96 ]. Also, comparison of expression pattern of several miRNAs in peripheral blood cells by qRT-PCR revealed a significant increase in the expression of miR-26a-5p in OCD patients compared to control subjects [ 97 ].…”