# Mechanisms of microRNA-mediated regulation of cellular proliferation in vascular malformations

> **NIH NIH P20** · ARKANSAS CHILDREN'S HOSPITAL RES INST · 2021 · $243,290

## Abstract

Vascular malformations are congenital anomalies of the lymphatic or vascular endothelial system and are characterized by a hyperproliferative phenotype of endothelial cells, which leads to the formation of ectatic veins, arteries, and lymphatic channels. These lesions can cause significant morbidity due to their propensity to enlarge, encroach on nearby anatomical structures, hemorrhage, become infected, cause significant pain and disfigurement, and divert blood supply from vital organs. Treatments for these lesions has traditionally relied on surgical excision or sclerotherapy, which have high rates of recurrence and complications. Several somatic, gain-of-function mutations in genes which control proliferation have been implicated in the endothelium of these lesions, making these genes and their downstream signaling cascades attractive targets for molecular pharmacotherapies. In preliminary experiments, we have identified microRNA-21 (miR-21), a known regulator of endothelial cell proliferation, as upregulated in lymphatic malformation tissue, leading to hyperphosphorylation of MAPK and increased cell growth. In this proposal, we will determine the entire miRNA expression profile of vascular malformation tissue and endothelial cells to identify all aberrantly expressed miRNAs and determine 
their effects on cellular proliferation and abnormal vessel formation. We will utilize previously collected frozen tissue specimens, freshly harvested vascular anomaly tissue and isolated endothelial cells, and existing normal endothelial cell lines which will undergo miRNA sequencing, proteomics analysis, and in vitro and in vivo growth assays. The long term goals are to identify potential miRNA-based treatments which target vascular anomaly endothelial proliferation and identify circulating biomarkers of vascular anomalies which are useful for diagnostics and treatment monitoring.

## Key facts

- **NIH application ID:** 10424618
- **Project number:** 5P20GM121293-05
- **Recipient organization:** ARKANSAS CHILDREN'S HOSPITAL RES INST
- **Principal Investigator:** GRAHAM M STRUB
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,290
- **Award type:** 5
- **Project period:** 2021-07-01 → 2022-07-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424618

## Citation

> US National Institutes of Health, RePORTER application 10424618, Mechanisms of microRNA-mediated regulation of cellular proliferation in vascular malformations (5P20GM121293-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10424618. Licensed CC0.

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