Back to 2014 Annual Meeting Abstracts

Background: Aberrant lymphatic development is believed to result in lymphatic malformations (LM), benign vascular anomalies that consist of dilated lymphatic vessels that are disconnected from the rest of the lymphatic system. These lesions grow significantly in size over time as extracellular fluid accumulates, potentially resulting in infection or impairment of neighboring structures. Unfortunately, the underlying etiology of LMs is still at large, which has hindered the development of more advanced, possibly less invasive approaches to managing this disease.
MicroRNA’s (miRNA’s) are short (19-22 nucleotides), non-coding, single strands of RNA that post-transcriptionally repress protein expression. They have been found to regulate a vast array of cellular pathways. Given their broad involvement in cell biology and human disease, we sought to characterize the miRNA expression profiles of 12 human lymphatic malformations.
Methods: RNA was extracted from human LM specimens and control human lymphatic endothelial cells for microarray analysis. miRNA databases were queried for several genes known to be involved in lymphangiogenesis-Prox1, GATA2, FOXC2, VEGC, VEGFR3, and LYVE1. These databases use bioinformatics to predict the miRNA regulators of a given gene. These miRNA’s were cross-referenced with our list of aberrant miRNA’s to identify miRNA that could be involved in LM development.
Results: We identified the top ten most up-regulated and down-regulated miRNA’s from 12 human LM specimens. Of these miRNA’s, only two were predicted to regulate a gene known to be involved in lymphagiogenesis. miR-181b-5p was found to be expressed at significantly lower levels than controls and is a regulator of Prox1. On the other hand, miR-551b-3p was significantly up-regulated and predicted to regulate GATA2. Other miRNA’s were identified as regulators of genes associated with lymphangiogenesis that are also aberrantly expressed in the LM specimens we analyzed.
Conclusions: This miRNA screen provides clues to better understand LM biology and the role of miRNA in lymphatic development. More in-depth bioinformatics are needed to delineate the specific pathways that might be altered by these miRNAs as well as additional in vitro studies assessing the significance these miRNA’s might have on a cellular level.