High-throughput RNA-sequencing reveals novel targets of tofacitinib in the treatment of rheumatoid arthritis.

OBJECTIVES: Although tofacitinib has been confirmed to have good efficacy and safety in the treatment of rheumatoid arthritis (RA), the relevant mechanism at the whole transcriptome level has not yet been revealed. In this study, peripheral blood mononuclear cells (PBMCs) from patients with active RA before and after tofacitinib treatment were analysed using whole transcriptome sequencing technology. METHODS: Fourteen patients with active RA were selected to detect the alterations of mRNAs, lncRNAs, circRNAs, and miRNAs in PBMCs before and after tofacitinib treatment using whole transcriptome sequencing. Through bioinformatics analysis, differentially expressed RNAs and their functions were identified. Then the competitive endogenous RNA (ceRNA) network and the protein interaction network were constructed. And qRT-PCR validation was performed for RNAs in the ceRNA network. RESULTS: Based on 69 DEmRNAs, 1743 DElncRNAs, 41 DEcircRNAs, and 4 DEmiRNAs obtained from whole transcriptome sequencing, an RNA interaction network including mRNA DEPDC1, lncRNA ENSG00000272574, circRNA hsa_circ_0034415, miR-190a-5p, and miR-1298-5p was constructed according to ceRNA theory. The qRT-PCR validation results of DEPDC1, hsa_circ_0034415 and miR-1298-5p involved in the network were consistent with the sequencing results, which provided important research evidence for further study of these RNAs. CONCLUSIONS: The new discovered circRNA/lncRNA-miRNA-mRNA network in RA patients relevant to tofacitinib therapy will provide new enlightenment for the role of tofacitinib in the treatment of RA and shed light on a new direction for further exploring the deep-seated mechanism of this drug.