A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

Abstract

Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the role of copy number variants (generally deletions) and certain alleles of common single nucleotide polymorphisms in the pathogenesis of schizophrenia. This disorder predominantly follows the polygenic inheritance model. Schizophrenia has also been linked with various alterations in the transcript and protein content of the brain tissue. Recent studies indicate that alterations in non-coding RNAs (ncRNAs) signature underlie a proportion of this dysregulation. High throughput microarray investigations have demonstrated momentous alterations in the expression of long non-coding RNAs (lncRNA) and microRNAs (miRNAs) in the circulation or post-mortem brain tissues of patients with schizophrenia compared with control samples. While Gomafu, PINT, GAS5, TCONS_l2_00021339, IFNG-AS1, FAS-AS1, PVT1, and TUG1 are among down-regulated lncRNAs in schizophrenia, MEG3, THRIL, HOXA-AS2, Linc-ROR, SPRY4-IT1, UCA1, and MALAT1 have been up-regulated in these patients. Moreover, several miRNAs, such as miR-30e, miR-130b, hsa-miR-130b, miR-193a-3p, hsa-miR-193a-3p, hsa-miR-181b, hsa-miR-34a, hsa-miR-346, and hsa-miR-7 have been shown to be dysregulated in blood or brain samples of patients with schizophrenia. Dysregulation of these transcripts in schizophrenia not only provides insight into the pathogenic processes of this disorder, it also suggests these transcripts could serve as diagnostic markers for schizophrenia. In the present paper, we explore the changes in the expression of miRNAs and lncRNAs in patients with schizophrenia.

Deregulatory miRNA-BDNF Network Inferred from Dynamic Expression Changes in Schizophrenia

“…A thorough understanding of transcription factors-miRNA-target gene axis may provide important clues to the molecular pathogenesis of SZ [ 16 , 49 ]. Of note, alterations within co-expression networks may occur with or without respective changes in the levels of its constituents.…”

“…As a diverse but specific set of mRNA expression silencers, miRNAs regulate the expression of numerous genes and are considered to be vital regulators in neurodevelopment [ 14 , 15 ]. A large number of studies have shown that miRNA expression is abnormal in the brain and the peripheral blood of patients with SZ [ 16 , 17 ]. Several miRNAs, such as miR-124, miR-132, miR-134, and miR-137, have been reported to be associated with SZ [ 18 ].…”

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

“…Pier Paolo Pandolfi and colleagues recommended a novel regulatory mechanism, known as competing endogenous RNA (ceRNA), in 2011 21 . It was suggested that cross-talk between both coding and non-coding RNAs such as lncRNAs, circular RNAs (circRNAs), and pseudogenes via miRNA response elements (MREs), as miRNA complementary sequences, leads to the formation of a large-scale regulatory network in diverse parts of the transcriptome 22 . According to the ceRNA hypothesis, RNAs transcripts can regulate each other by competing for shared miRNAs.…”

Inferring miRNA sponge modules across major neuropsychiatric disorders

“…The lncRNA MEG3 from module 7 functions as a ceRNA in ischemia-induced neuronal cell apoptosis (Liu et al, 2016 ). MEG3 is upregulated, and PINT (from module M10) is downregulated in SCZ post-mortem brain samples (Ghafouri-Fard et al, 2021 ).…”