Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis

Area of Science:

• Genetics and Epigenetics
• Immunology
• Molecular Biology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease influenced by genetic, environmental, and epigenetic factors.
• Long non-coding RNAs (LncRNAs) are crucial epigenetic regulators implicated in autoimmune disease development.

Purpose of the Study:

• To identify differentially expressed LncRNAs (DE-LncRNAs) functionally linked to genes modulated in RA.
• To elucidate the role of specific DE-LncRNAs in RA pathogenesis.

Main Methods:

• Transcriptome profiling of peripheral blood mononuclear cells (PBMCs) from early RA patients and healthy donors using Clariom D arrays.
• Validation of DE-LncRNA targets and their association with differentially expressed genes (DEGs) in RA using real-time PCR.

Main Results:

• Six DE-LncRNAs were identified, targeting microRNAs that regulate RA-associated DEGs.
• RP11-498C9.15 targeted numerous DEGs, enriched RA-associated signaling pathways, and highly connected genes in the RA interactome.
• FTX and HNRNPU-AS1 also targeted a substantial number of DEGs.

Conclusions:

• RP11-498C9.15 may play a pivotal role in RA pathogenesis by modulating microRNAs and gene expression.
• The identified DE-LncRNAs, particularly RP11-498C9.15, represent potential therapeutic targets for rheumatoid arthritis.