Exploring gene expression, alternative splicing events and RNA-binding proteins changes in PBMC from patients with hyperuricemia

Aim

The objective of this study was to examine the transcriptomic profile changes in hyperuricemia (HUA) and to investigate the pathogenic mechanisms and biomarkers of HUA from a transcriptomic perspective.

Methods

In this study, three patients with HUA were randomly selected and matched with three healthy controls. Six participants provided peripheral blood mononuclear cells (PBMCs) for analysis. RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) and alternative splicing events (ASEs). Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify the functions and pathways of the DEGs and ASEs. Additionally, a co-expression network was constructed to analyze the regulation of DEGs and ASEs by RNA-binding protein (RBP) genes. In addition, important DEGs and ASEs were validated using quantitative real-time PCR (qPCR).

Results

There were 633 DEGs identified, 348 up-regulated DEGs and 285 down-regulated DEGs, including RGS18, CAVIN2, GZMH, GNLY and MT-TV, which were mainly enriched in inflammatory and immune-related biological processes. A total of 1542 ASEs were significantly differentially expressed in HUA, of which LTB4R and ENTPD4 were closely associated with the development of HUA. In addition, 15 RBP genes were detected to be differentially expressed in HUA. Three RBP genes (IFIT1, IFFIT2, and IFIT3) were highly associated with immunoinflammation and affected HUA by modulating downstream immune responses, inflammatory response-associated DEGs, and ASEs. The selected five DEGs and two ASEs were verified by qPCR, which was consistent with the results of RNA sequencing.

Conclusions

In summary, the findings indicate that HUA is associated with significant changes in inflammatory and immune response-related genes (RGS18, CAVIN2, GZMH, GNLY, MT-TV, LTB4R, ENTPD4, IFIT1, IFFIT2, and IFIT3). These findings suggest potential biomarkers and therapeutic targets.