Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment‑resistant schizophrenia using miRNA sequencing and integrated bioinformatics

Abstract

Treatment-resistant schizophrenia (TrS) is a common phenotype of schizophrenia that places a considerable burden on patients as well as on society. TrS is known for its tendency to relapse and uncontrollable nature, with a poor response to antipsychotics other than clozapine. Therefore, it is urgent to identify objective biological markers, so as to guide its treatment and associated clinical work. in the present study, the peripheral blood mononuclear cells (PBMcs) of patients with TrS and a healthy control group, which were gender-, age-and ethnicity-matched, were subjected to microrna (mirna/mir) sequencing to screen out the top three mirnas with the highest fold change values. These were then validated in the TrS (n=34) and healthy control (n=31) groups by reverse transcription-quantitative Pcr. For two of the top three mirnas, the Pcr results were in accordance with the sequencing result (P<0.01), while the third mirna exhibited the opposite trend (P<0.01). To elucidate the functions of these two mirnas, Homo sapiens (hsa)-mir-218-5p and hsa-mir-1262 and their regulatory network, target gene prediction was first performed using online TargetScan and diana-micro T software. Bioinformatics analysis was then performed using functional enrichment analysis to determine the Gene ontology terms in the category biological process and the Kyoto encyclopedia of Genes and Genomes pathways. it was revealed that these target genes were markedly associated with the nervous system and brain function, and it was obvious that the differentially expressed mirnas most likely participated in the pathogenesis of TrS. a receiver operating characteristic curve was generated to confirm the distinct diagnostic value of these two mirnas. it was concluded that aberrantly expressed mirnas in PMBcs may be implicated in the pathogenesis of TrS and may serve as specific peripheral blood-based biomarkers for the early diagnosis of TrS.

miR - 218 - 2 regulates cognitive functions in the hippocampus through complement component 3–dependent modulation of synaptic vesicle release

“…Recently, miR-218 has been suggested to show abnormal expression in a variety of neurodegenerative and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, depression, and anxiety (19)(20)(21)(22)(23)(24). miR-218 includes miR-218-1 and miR-218-2, which are located in the introns of the tumor suppressor genes SLIT2 and SLIT3, respectively (25).…”

Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives

“…We also found some evidence that involves epigenetics including DNA methylation and microRNAs (miRNAs) (You et al, 2020;Hannon et al, 2021). One concrete example was the ribonuclease DICER1, which plays a key role in the production of miRNAs.…”

“…In comparison to the healthy group, DICER1 genes were increased in the TRS group ( Moretti et al, 2018 ). The top three miRNAs with the highest fold change values were screened out from peripheral blood mononuclear cells, hsa-mir-218-5p and hsa-mir-1262 of them were biomarkers for an earlier and more accurate diagnosis of TRS ( You et al, 2020 ). It is interesting to note that, compared to non-TRS instances, TRS cases appear to have much greater proportions of granulocytes and lower proportions of CD8 + T-cells based on cellular composition variables derived from DNA methylation data.…”

Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review

“…DICER1 is a main component of the miRNA biogenesis machinery [ 70 ] and was upregulated in TRS patients [ 37 ]. Expression levels of multiple miRNAs were also elevated in TRS patients, including miR-181b-5p , miR-195-5p , miR-301a-3p [ 46 ], hsa-miR-218-5p , hsa-miR-1262 [ 47 ], and hsa-miR-675-3p [ 48 ].…”