Abstract
Background: The diagnosis of schizophrenia (SCZ) depends on the evaluation of clinical symptoms, and there is no objective biomarker. Surveys have found that long non-coding RNA (lncRNA) may be affected in the pathogenesis of SCZ. There are also different genes in the expression of peripheral blood (PBL) in SCZ patients.Methods: We profiled transcriptome analysis of PBL in 50 patients with schizophrenia and 50 controls without psychiatric diagnoses, reconstructed PBL transcriptome information using RNA-seq, predicted lncRNA-mRNA interaction via “RNAplex”, a hierarchical classification-Spielman correlation coefficient approach was used to analyze the correlation between lncRNA and protein-coding gene expression among samples, and used systematic bioinformatics methods (Go/Pathway) to perform lncRNA functional annotation and qPCR experimental verification. Predicting functional sites for sequences using the database PROSITE, NCBI, UCSC, JASPAR.Results: We screened 94 lncRNA and 1179 mRNA differential expressions in PBL, of which 46 new lncRNAs were identified for the first time. Enrichment into lncRNA involves biological processes and signaling pathways related to the neutrophil activation involved in immune response. According to Spearman correlation coefficient analysis, 81 lncRNA and 410 mRNA have expression correlation (p<0.01 and |r|≥0.4), QPCR in independent samples verified that the core node of the lncRNA-mRNA co-expression network IL1RAP-TCONS_00138311 variable shear is indeed highly expressed in SCZ patients, 2^-△△Ct is 0.56, the area under the ROC curve is 0.924. The top four ranked transcription factors were predicted to be HSF1, HSF2, HSF4, and FOXA1.Conclusions: Combined with sequence function analysis, it showed that the transcription factors FOXA1, HSF1, HSF2, HSF4, etc. may mediate the activation of IL1B-induced NF-kβ pathway and other inflammatory pathways through the regulation of IL1RAP alternative splicing transcripts TCONS_00138311, thereby participating in the pathogenesis of SCZ. We propose that the frequency of Differential lncRNA in peripheral blood could be used as novel biomarker for distinguishing SCZ from health.
Improved anatomic delineation of the antidepressant response to partial sleep deprivation in medial frontal cortex using perfusion-weighted functional MRI
