Objective: Considering the molecular complexity and heterogeneity of rheumatoid
arthritis (RA), the identification of novel molecular contributors involved in RA initiation and
progression using systems biology approaches will open up potential therapeutic strategies. The
bioinformatics method allows the detection of associated miRNA-mRNA as both therapeutic and
prognostic targets for RA.
Methods: This research used a system biology approach based on a systematic re-analysis of the
RA-related microarray datasets in the NCBI Gene Expression Omnibus (GEO) database to find out
deregulated miRNAs. We then studied the deregulated miRNA-mRNA using Enrichr and
Molecular Signatures Database (MSigDB) to identify novel RA-related markers followed by an
overview of miRNA-mRNA interaction networks and RA-related pathways.
Results: This research mainly focused on mRNA and miRNA interactions in all tissues and
blood/serum associated with RA to obtain a comprehensive knowledge of RA. Recent systems
biology approach analyzed seven independent studies and presented important RA-related
deregulated miRNAs (miR-145-5p, miR-146a-5p, miR-155-5p, miR-15a-5p, miR-29c-3p, miR-
103a-3p, miR-125a-5p, miR-125b-5p, miR-218); upregulation of miR-125b is shown in the study
(GSE71600). While the findings of the Enrichr showed cytokine and vitamin D receptor pathways
and inflammatory pathways. Further analysis revealed a negative correlation between the vitamin
D receptor (VDR) and miR-125b in RA-associated gene expression.
Conclusion: Since vitamin D is capable of regulating the immune homeostasis and decreasing the
autoimmune process through its receptor (VDR), it is regarded as a potential target for RA.
According to the results obtained, a comparative correlation between negative expression of the
vitamin D receptor (VDR) and miR-125b was suggested in RA. The increasing miR-125b
expression would reduce the VitD uptake through its receptor.