Identification of PBMC-expressed miRNAs for rheumatoid arthritis

ABSTRACT

Post-transcriptional regulation by miRNAs plays an important role in the pathogenesis of rheumatoid arthritis (RA), however, the roles of specific miRNAs in RA pathogenesis remain largely unclear. This study performed dual-omics (miRNA and mRNA) integration analysis and in-depth cellular and molecular functional exploration to identify novel RA-associated miRNAs and to understand their underlying pathogenic mechanism. Based on the miRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from a discovery sample set (25 RA cases and 18 healthy controls), 18 differentially expressed miRNAs (DEMIRs) (|Fold-change|>2 and P < 0.05) were identified and corresponding interaction networks of DEMIRs and mRNA were constructed. After the expression validation of the DEMIRs in a validation sample set (35 RA cases and 35 healthy controls), miR-99b-5p was highlighted. The over-expression of newly discovered miR-99b-5p is able to suppress T cell apoptosis, promote cell proliferation and activation, increase expression of proinflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ), and inhibit expression of its target genes mTOR and RASSF4. This study comprehensively identified PBMC-expressed miRNAs along with corresponding regulatory networks significant for RA and discovered miR-99b-5p as a novel post-transcriptional mediator involved in RA pathogenesis. The findings improved our understanding of RA pathogenesis and provided novel insights into the molecular mechanisms underlying RA pathogenesis.

KEYWORDS:

• Rheumatoid arthritis
• miRNA
• miR-99b-5p

Authors’ contributions

XZ, LW and SL designed the study. XZ, LW, WX, YG, MW, KZ, JW, YQ, XLin and XLu collected the data. XZ, LW, XM and WX were involved in data cleaning and data analysis. XZ drafted the manuscript. LW, FD and SL contributed to data interpretation, critical revision of the manuscript for important intellectual content, and approved the final version of the manuscript. All authors have read and approved the final manuscript.

Acknowledgments

We thank the help from Mr. Amanda Hall Pendegraft (The University of Alabama at Birmingham, USA) for fixing the typos and grammar errors.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by grants from the National NaturalScience Foundation of China (81473046, 81872681, 31401079, 56581373010, 81502868, 81401343, 81541068), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (16KJA330001), a Project of thePriority Academic Program Development of Jiangsu Higher Education Institutions and a Project of Entrepreneurship andInnovation of Jiangsu Province.