Effective Diagnostic Biomarkers, Immune Infiltration, miRNA and N6-methyladenosine regulators in Lupus Nephritis

Abstract

Objective Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE), which is an autoimmune disease involving multiple organs. This study aimed to explore the potential molecular mechanism of LN by bioinformatic analysis. Method In total, 130 LN, 25 living healthy donors were included to explore the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of DEGs were developed using the STRING database. Additionally, five algorithms were used to find the hub genes and their diagnostic effectiveness was predicted using receiver operator characteristic curve (ROC) analysis. CIBERSORT was used to evaluate the infiltration of immune cells in LN. Furthermore, the mRNA-miRNA network was constructed. Finally, we explored the landscape of N6-methyladenosine (m6A) regulators in LN. Result Two hub genes—FOS and IGF1—were found by the intersection of five different algorithms. FOS and IGF1 could jointly diagnose LN with the most excellent specificity and sensitivity. LN patients had lower activated and resting dendritic cells (DCs) while higher M1 macrophages and activated NK cells than HC. FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. MiR-155 is considered as the hub miRNA. And m6A modification is related to the severity of renal injury and involved in the pathogenesis of LN. MiRNA may affect the occurrence and development of LN by targeting m6A regulators. Conclusion Activated DCs, resting DCs, M1 macrophages, and activated NK cells may play a role in LN pathogenesis. FOS, IGF1 and miR-155 may be new potential molecular markers for the pathogenesis, progression and new molecular targets for treatment of LN. MiRNA may affect the occurrence and development of LN by targeting m6A regulators.

Understanding the interplay between N6‐methyladenine RNA methylation and noncoding RNAs in kidney disease

“…Among existing miRNAs, miR-155 is a potential new biomarker for monitoring the progression of lupus nephritis (LN) and may impact the occurrence and development of LN by targeting m 6 A regulators. 9 In kidney clear cell carcinoma, miR-155 negatively regulated 3′ UTR of mRNA of FTO, an eraser of m 6 A, which increased m 6 A level, reduced apoptosis, and enhanced tumour cell proliferation. 10 Similarly, miR-501-3p was also reported to inhibit kidney cancer cell proliferation by targeting WTAP and decreasing the level of m 6 A.…”

“…Unfortunately, the current evidence of miRNAs regulating m 6 A modification in non‐tumor kidney diseases is not robust. Among existing miRNAs, miR‐155 is a potential new biomarker for monitoring the progression of lupus nephritis (LN) and may impact the occurrence and development of LN by targeting m 6 A regulators 9 . In kidney clear cell carcinoma, miR‐155 negatively regulated 3′ UTR of mRNA of FTO, an eraser of m 6 A, which increased m 6 A level, reduced apoptosis, and enhanced tumour cell proliferation 10 .…”