RNA-seq analysis reveals altered gene expression profiles in HMEC-1 cells overexpressing KRAS gene associated with
Kexin Yuan1, Yahui Zhao2, Haibin Zhang2
1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Dongcheng District, Beijing, China.
Background:
Brain arteriovenous malformation (bAVM) is a rare vascular disorder that can lead to severe neurological symptoms. The molecular mechanisms driving bAVM development and progression of bAVM remain poorly understood. This study aimed to investigate the molecular changes potentially associated with bAVM pathogenesis by performing RNA-seq on human microvascular endothelial cells (HMEC-1) overexpressing KRAS, a key driver of BAVM.
Results:
HMEC-1 cells overexpressing KRAS were established as an in vitro model of bAVM. RNA-seq were conducted and transcriptomic analysis revealed that differentially expressed genes in HMEC-1 cells overexpressing KRAS were predominantly enriched in pathways related to cell adhesion, signaling, and transport, which may contribute to bAVM pathogenesis. Specifically, upregulated genes were mainly located in the cell-substrate junctions and focal adhesion, whereas downregulated genes were primarily located in the ribosomal subunits, ribosome, mitochondrial protein complex, and mitochondrial inner membrane.
Conclusions:
Our findings provided a preliminary delineation of molecular mechanisms after KRAS overexpression in endothelial cells, which may contribute to the development of bAVM. Future work will focus on validating these results in clinical specimens, functionally characterizing the dysregulated pathways, and exploring their potential as novel therapeutic targets.
