Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation.

Drug Des Devel Ther

Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China.

Published: September 2024

AI Article Synopsis

  • - Infantile Hemangioma (IH) is a common, benign tumor in infants, and understanding its causes is still unclear, prompting a study that used data analysis to uncover potential treatments.
  • - The researchers identified over 1,200 genes involved in IH and pinpointed 100 key genes using various computational methods, including drug repurposing from existing databases.
  • - Twelve drugs, including agents like dasatinib and sirolimus, showed potential in lab tests as they inhibited growth and encouraged cell death in IH-related cells, indicating their therapeutic prospects.

Article Abstract

Introduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology.

Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD).

Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the , and signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value.

Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the , and signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404501PMC
http://dx.doi.org/10.2147/DDDT.S460575DOI Listing

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