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Comprehensive analysis of circRNA expression profiles and circRNA associated competing endogenous RNA networks in IgA nephropathy

ABSTRACT: Purpose: Immunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide, the exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA, microRNA (miRNA), and messenger RNA (mRNA) ceRNA network in peripheral blood mononuclear cells (PBMCs) of IgAN. Methods: CircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls. A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Results: A total of 145 circRNAs were differentially expressed in IgAN compared with controls (|log2 (FC)|>1 and P-value <0.05). Combined with the data from GSE73953 and GSE25590 in GEO database, a ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). Conclusion: Our study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154046 | GEO | 2020/11/08

REPOSITORIES: GEO

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Project description:Background: Atrial fibrillation (AF), a critical health and economic issue is common in patients with heart failure (HF). Meanwhile, HF is a leading complication of nonvalvular atrial fibrillation (NVAF), and the presence of both conditions is associated with worsen outcomes. Accumulating evidence has indicated that messenger RNA (mRNA), microRNA (miRNA) and circular RNA (circRNA) play vital roles in the occurrence and progression of HF and AF. However, the underlying molecular mechanism of HF with AF remains elusive. We aimed to investigate the role of circRNA/miRNA/mRNA regulatory network in HF with AF through High-throughput sequencing and bioinformatics analysis. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 4 patients who had heart failure with atrial fibrillation (HF /AF group) and 4 matched healthy subjects. RNA sequencing was performed to get circRNAs and mRNAs. miRNAs were obtained through miRanda and HMDD databases. qRT-PCR was used to verify our data. R software was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The PPI network was completed using STRING. Immune infiltration analysis was performed using cibersort method. The ceRNA network of circRNA/miRNA/mRNA was constructed by Cytoscape. Results: Differential expression analysis showed that circRNAs (137 upregulated and 31 downregulated) and mRNAs (534 upregulated and 255 downregulated) were considered as significantly different between HF with AF group and control group. Immune infiltration analysis demonstrated that macrophages were obviously upregulated and mast cells were significantly downregulated in PBMCs of the HF/AF group. GO and KEGG analyses showed that HF with AF-related mRNAs were abundant in the pathway of programmed cell death (PCD) and myocardial remodeling. So we confirm that hsa_circ_0047870/hsa-miR-34a-5p/SMPD1, hsa_circ_0127340/hsa-miR-192-3p/FBXW5, hsa_circ_0002484/hsa-miR-26b-3p/PYCARD, hsa_circ_0047870/hsa-miR-20b-3p/HTRA2 and hsa_circ_0004027/hsa-miR-26a-5p/HIF1A ceRNA axes could promote the development of HF with AF through the PCD-related pathway. Conclusions: We suggested that the imbalance of immune cell composition in PBMCs may play an initial role in the progression of HF with AF. The PCD-related ceRNA regulatory network may be the potential therapeutic target in the occurrence and progression of HF with AF. The circRNAs could serve as novel diagnostic markers.

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Comprehensive analysis of circRNA expression profiles and circRNA associated competing endogenous RNA networks in IgA nephropathy

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