Exploring the Potential of lncRNAs as Biomarkers for Rheumatoid Arthritis

Long noncoding RNAs, also known as lncRNAs, are a large and diverse class of transcribed RNA molecules that are longer than 200 nucleotides and do not code for proteins. Currently, around 35,000 lncRNAs exist in the human genome and are part of the regulatory class of RNAs. Some of these lncRNAs have been fully characterized and take part in gene inhibition or gene activation in mechanisms relating to chromatin modification and structure, direct transcriptional regulation, RNA processing events, protein activity and localization, modulation of microRNs, and gene silencing.

It is no surprise given the complex involvement of lncRNAs in gene regulation that lncRNAs contribute to the development of various human diseases. For example, in some cancers lncRNAs promote proliferation, invasion, and metastasis of cancer cells. In addition, lncRNAs have been shown to play a regulatory role in the immune cells of the innate immune system and are involved in the pathogenesis of several autoimmune diseases such as rheumatoid arthritis (RA).

Predominately occurring in women, RA is a chronic, progressive, and disabling autoimmune disease in which the body’s immune system mistakenly attacks the joints, resulting in swelling and pain. In an article published in PLOS One, the authors explore peripheral blood mononuclear cell (PBMC) lncRNAs involvement in rheumatoid arthritis (RA) of female patients. More specifically, the authors aim to find a potential biomarker for the assessment and diagnosis of RA patients.

To paint a broader picture of what is going on within the PBMCs of female RA patients, the authors used bioinformatics to identify differentially expressed (DE) lnc-RNAs. Of the analysis, 2,099 DE-lncRNAs were differentially expressed with 683 upregulated and 1,416 downregulated, many of which were in close proximity to their differentially expressed neighboring protein-coding genes. Analysis of the DE-mRNA for these coding genes also revealed expression differences as compared to controls. Upon narrowing down the DE-lncRNAs, real-time qPCR showed that 4 DE-lncRNAs had significant changes in their expression levels. One candidate strongly correlated with serum levels of IL-6 and TNF- and the Simplified Disease Activity Index (SDAI) of the RA patients, suggesting that this candidate may be a potential biomarker for the assessment and diagnosis of RA patients.

Recent analysis into lncRNA-disease associations and predicting potential lncRNA-disease associations have become increasingly important, as well as the potential of these In this study, the authors describe a possible candidate, ENST00000456270, as a biomarker for RA patients. This finding may lead to a means of predicting the susceptibility, diagnosis, prognosis, and treatment of RA.

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