Implication of LncRNAs MEG3 and LINC00305 in Pathophysiological Mechanisms associated with Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Early diagnosis and early and effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Complex interplay between multiple risk factors contributes to RA. These risk factors include environmental factors, genetic factors and epigenetic modifications. Long non-coding RNAs (lncRNAs) are involved in these epigenetic mechanisms. Accumulating evidence has shown that lncRNAs participate in the processes of inflammation, aberrant proliferation, apoptosis and angiogenesis. They also play roles in autoimmune diseases, such as SLE, Sjogren syndrome, RA and multiple sclerosis. Maternally expressed gene 3 (MEG3) is a maternally expressed lncRNA of the imprinted DLK1–MEG3 locus located on human 14q32 chromosome. It functions as a tumor suppressor. Decreased MEG3 expression has been observed in various human cancers, both type 1 and type 2 diabetes, osteoarthritis and in RA. Decreased serum levels of lncRNA MEG3 in RA could be attributed to MEG3 promoter hypermethylation induced by hypoxia. This downregulation was associated with increased inflammation, cell proliferation and cell invasion and decreased apoptosis. Long intergenic non-Protein coding RNA 00305 (LINC00305) was identified as a pro-inflammatory atherosclerosis-associated lncRNA. RA was associated with increased LINC00305 which served as a regulator of inflammatory, hypoxic, invasive, apoptotic and proliferative mechanisms associated with RA.