Diagnostic Biomarker Hsa_circ_0126218 and Functioning Prediction in Peripheral Blood Monocular Cells of Female Patients With Major Depressive Disorder

Abstract

IntroductionAlthough major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis.MethodsFirst, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out.ResultsThere is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226–0.8791, p < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork.Conclusionhsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.

The role of ncRNAs in depression

“…It has been hypothesised that circRNAs bind to miRNAs as a chelator and further influence the expression of several factors that influence depression, such as mRNA stability, resulting in depressive-like behaviour [ 143 , 144 ]. The former study demonstrated that microglia transfer a microglia-enriched microRNA, miR-146a-5p, by secreting exosomes to improve neurogenesis and depression-like behaviour.…”

Circular RNAs: New players involved in the regulation of cognition and cognitive diseases

“…Emerging studies have shown that circRNAs may be involved in the onset and progression of depression, so they have become a promising new field in the diagnosis of depression. Reports have shown that hsa_circRNA_103636 ( Cui et al, 2016 ), hsa_circ_0126218 ( Bu et al, 2021 ), circFKBP8 ( Shi et al, 2021 ), circMBNL1 ( Shi et al, 2021 ), and circDYM ( Song et al, 2020 ) might be promising MDD biomarkers, which may further improve the early detection, effective diagnosis, and convenient monitoring of MDD. However, at present, the diagnostic accuracy and specificity of these circRNAs still need to be verified by multicenter and large samples.…”

Research Progress of circRNAs in Glioblastoma

“…Nowadays, there are more and more researches on the mechanism of circRNAs generation. In addition to RBP can bind to circRNAs to reduce the regulation of RBP on target genes and affect tumorigenesis (Huang C.-K. et al, 2020;Li et al, 2020;Song et al, 2021), some RBP can also regulate the generation of circRNAs, which also has an important role in tumor development (2016;Liu Z. et al, 2021;Wang et al, 2021d;Wang and Lei, 2021;Yang T. et al, 2021). The translation function of circRNAs is also becoming a hot topic, and the translation initiation mechanism of circRNAs mainly includes cap-dependent, IRES-dependent, m6adependent and small ORF-dependent translation initiation (He L. et al, 2021;Wang X. et al, 2021), and circRNAs encode proteins with the function of suppressing tumor activity and protecting proteins from degradation (Chen C.-K. et al, 2021;Wang et al, 2021d;Ma et al, 2021;Qi et al, 2021).…”

“…Studies have shown that circRNAs are abundant and stable in exosomes, and some circRNAs are more highly expressed in blood than in tissues ( D'Ambrosi et al, 2021 ; Reese and Dhayat, 2021 ; Tian et al, 2021 ; van Zonneveld et al, 2021 ). The high expression and stability of circRNAs in body fluids would be more beneficial for their clinical applications ( Bu et al, 2021 ; Fontemaggi et al, 2021 ; Wang et al, 2021h ; Zhao et al, 2021 ). However, despite the identification of thousands of tissue- and disease-specific circRNAs by RNA-seq ( Kaushik et al, 2021 ; Tian-Zhao et al, 2021 ), the understanding of the mechanism of circRNAs generation and biological functions is limited at this stage.…”