Identification of Key Ubiquitination-Related Genes and Their Association with Immune Infiltration in Osteoarthritis Based on the mRNA-miRNA Network.

ABSTRACT

Osteoarthritis (OA) is a prevalent degenerative joint disease that is closely associated with functions of ubiquitination and immune cells, yet the mechanism remains ambiguous. This study aimed to find core ubiquitination-related genes and their correlative immune infiltration in OA using weighted gene co-expression network analysis (WGCNA). The ubiquitination-related genes, datasets GSE55235 and GSE143514 were obtained from open databases. WGCNA got used to investigate key co-expressed genes. Then, we screened differentially expressed miRNAs by "limma" package in R, and constructed mRNA-miRNA network. We conducted function enrichment analysis on the identified genes. CIBERSORT was then utilized to analyze the relevance between immune infiltration and genes. Lastly, RT-qPCR was further used to verify the prediction of bioinformatics. A sum of 144 ubiquitination-related genes in OA were acquired. Enrichment analysis indicated that obtained genes obviously involved in mTOR pathway to regulate the OA development. GRB2 and SEH1L and L-arginine synergistically regulate the mTOR signaling pathway in OA. Moreover, GRB2 and SEH1L were remarkably bound up with immune cell infiltration. Additionally, GRB2 expression was upregulated and SEH1L level was downregulated in the OA development by RT-qPCR experiment. The present study identified GRB2 and SEH1L as key ubiquitination-related genes which were involved in immune infiltration in OA patients, thereby providing new drug targets for OA.