PRS AAPS Oral Proofs 2016
Brandon J. Sumpio, BA, Brent Schultz, MD, Andre Alcon, MD, Deepak Narayan, MD
From the Yale University School of Medicine, New Haven, Conn.
PURPOSE: Lymphatic malformations (LMs) are dilated lymphatic vessels that are disconnected from the rest of the lymphatic system. The underlying etiology of LMs are still at large. MicroRNAs (miRNAs) are short, noncoding, single strands of RNA that posttranscriptionally repress protein expression and are involved in a majority of human physiology. By characterizing the miRNA expression profiles of LMs, we seek to better understand the disease.
METHODS: RNA was extracted from human LM specimens and control human lymphatic endothelial cells for microarray analysis. miRNA bioinformatic databases were used to predict miRNA regulators. Pathway analysis was performed using Qiagen Ingenuity Pathway Analysis (Redwood City, Calif.).
RESULTS: Two of these—miR-181b-5p and miR-551b-3p—are predicted to regulate genes involved with LMs and lymphangiogenesis, respectively. Pathway analysis of the miRNA data shows inhibition of the CD36 pathway. CD36 has a thrombospondin-1 receptor that functions to inhibit lymphangiogenesis through the inhibition of VEGF-c and VEGF-d expression in lymphatic channels.
CONCLUSIONS: We have identified miRNAs that may play a role in pathogenesis and in identifying a pathway that could serve as a novel drug target.