Understanding Juvenile Arthritis: The Role of MicroRNAs

Abstract

By Divya Takkellapati, Biological Sciences

Advisor: Grant Schulert

Presentation ID: PM_D17

Abstract: MicroRNAs are small, noncoding RNAs with a powerful function: they can control which genes are ultimately expressed in the body. One group of microRNAs, the miR-17-92 cluster, has already been widely studied for its role in cancer. Interestingly, several members of miR-17-92 are highly expressed in immune cells called monocytes from patients with active Systemic Juvenile Idiopathic Arthritis (SJIA). SJIA is a chronic autoinflammatory disease in children; monocytes and their mature counterparts called macrophages are thought to be important in its pathogenesis. To determine the potential role of miR-17-92 in SJIA, I first measured miR-17-92 levels in monocytes and macrophages under various conditions. Then, I overexpressed miR-17-92 in monocytes and analyzed transcriptome sequencing data. I found the most sizable changes in miR-17-92 levels during the transition from monocyte to macrophage; 2-day old partially differentiated monocytes had slightly higher levels, while fully differentiated 7-day old macrophages had lower levels. Additionally, miR-17-92 overexpression resulted in increased expression of key inflammatory genes, including many involved in Type I and II interferon pathways. Taken together, SJIA monocytes may have a slightly more differentiated or mature phenotype, resulting in increased miR-17-92 and thus increased inflammatory characteristics.