Identification of miRNA-mRNA network and immune-related gene signatures in IgA nephropathy by integrated bioinformatics analysis

BMC Nephrology

Shang-Wei Ning¹  Shuang Guo¹  Bei Feng²  Xuan-Yi Du³  Shi-Yao Wei⁴ 

[1] College of Bioinformatics Science and Technology, Harbin Medical University, 157 Baojian Road, Nangang District, 150081, Harbin, Heilongjiang Province, China;Department of Nephrology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China;College of Bioinformatics Science and Technology, Harbin Medical University, 157 Baojian Road, Nangang District, 150081, Harbin, Heilongjiang Province, China;Department of Nephrology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, 150086, Harbin, Heilongjiang Province, People’s Republic of China;Department of Nephrology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, 150086, Harbin, Heilongjiang Province, People’s Republic of China;College of Bioinformatics Science and Technology, Harbin Medical University, 157 Baojian Road, Nangang District, 150081, Harbin, Heilongjiang Province, China;

关键词: CIBERSORT;    Hub genes;    IgA nephropathy;    Immune cells;    Immunotherapy;    microRNAs;   

DOI  :  10.1186/s12882-021-02606-5

来源: Springer

【 摘 要 】

BackgroundIgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration.MethodsThe expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein–protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells.ResultsFour downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration.ConclusionsA potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients.

【 授权许可】

CC BY