Bioinformatic Analysis of Differentially Expressed miRNAs in Egyptian Patients with Early Onset Rheumatoid Arthritis

Amr, Khalda S; Eltaweel, Noha H; Ismail, Sherif; Raslan, Hala Mohamed

doi:10.21608/ejchem.2024.292925.9773

Bioinformatic Analysis of Differentially Expressed miRNAs in Egyptian Patients with Early Onset Rheumatoid Arthritis

Document Type : Original Article

Authors

¹ Medical Molecular Genetics Department, Human Genetics and Genome Research institute of National Research Center, Cairo, Egypt

² Medical Molecular Genetics dept., Human genetics and genome project institute, NRC, EGYPT

³ Rheumatology and rehabilitation, Internal medicine department, medical research and clinical studies institute, National Research Center, Cairo, Egypt

⁴ internal medicine and rheumatology, Internal medicine department, medical research and clinical studies institute, National Research Center, Cairo, Egypt

10.21608/ejchem.2024.292925.9773

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the diarthrodial joints, causing joint destruction and irreversible joint damage. In this study, we aimed to identify the top deregulated miRNAs that might be related to RA pathogenesis followed by bioinformatic analysis to detect their target genes. The study included four RA patients and two healthy controls. Total RNA was isolated from plasma to be subjected to miRNAs profiling by next generation sequencing (NGS). Sequencing libraries were constructed and generated using the NEBNextR, UltraTM small RNA Sample Prep Kit for Illumina R (NEB, USA), according to the manufacturer’s instructions. Functional annotation of target genes was performed using Enrichr available at https://maayanlab.cloud/Enrichr/, and visualized using Appyter. The top upregulated miRNAs were: hsa-miR-6724-5p, hsa-miR-1469, hsa-miR-4632-5p, hsa-miR-3960, hsa-miR-6815-3p, hsa-miR-6823-3p, hsa-miR-10400-5p, hsa-miR-194-3p, hsa-miR-4301, hsa-miR-6758-5p, their predicted target hub genes were SH3TC2, TM9SF4, HDGF and GPAT4. The top downregulated miRNAs were: hsa-miR-1468-5p, hsa-miR-6510-3p, hsa-miR-6743-5p, hsa-miR-486-3p, hsa-miR-15b-3p, hsa-miR-128-3p, hsa-miR-328-3p, hsa-miR-4493, hsa-miR-4433a-3p, hsa-miR-4433b-5p, their predicted target hub genes were NPTXR, SZRD1, WEE1 and MKNK2. The selected pathways of RA-specific genes were mainly: RA KEGG pathway, IL-17 signaling pathway, Jak-STAT signaling pathway, TH-17 cell differentiation, and MAPK signaling pathway. The predicted target genes of the deregulated miRNAs were found to be involved in RA pathogenesis.

Keywords