Head of Lab Petrovsky National Research Center of Surgery Moscow, United States
Abstract: MicroRNAs (miRNAs) are critical regulators of gene expression involved in various biological processes, including angiogenesis, inflammation, cell proliferation, migration, and invasion. The present study aims to investigate the differential expression of miRNAs and their associated pathways in the EA.hy926 cell line exposed to low-density lipoproteins (LDL) and latex particles. The study was conducted using EA.hy926 cells subjected to three conditions: Control, LDL treatment, and Latex particles (Beads) treatment. MicroRNA expression was analyzed and compared between groups, and significant changes in expression were identified. Additionally, related genes, affected pathways, and predicted targets were investigated through literature analysis and experimental validation. The expression of miR-126 was downregulated upon exposure to both LDL and latex particles. The associated genes include IL-17A, caspase-3, and survivin, with the affected signaling pathway being PI3K/AKT/mTOR. Predicted targets of miR-126 are LRP1, LRP1B, LDLRAD2, STARD4, SEC14L1, and MSR1. Direct targets of miR-126 identified are LRP11 and VEGFB. In contrast to miR-126, the expression of miR-616 was upregulated upon exposure to LDL. The associated genes include MMP2, MMP9, and TIMP2, influencing processes such as cell proliferation, migration, and invasion. Predicted targets of miR-616 include TLR1, TNFSF14, TNFRSF11B, LILRB4, and ILDR2. However, no significant direct targets for miR-616 were identified in the present study. The study reveals distinct patterns of miRNA expression and their involvement in key signaling pathways associated with LDL and latex particle exposure. Downregulation of miR-126 and its involvement in the PI3K/AKT/mTOR pathway suggests potential modulation of angiogenesis and inflammation. The upregulation of miR-616 indicates enhanced cell migration and invasion pathways. Further experimental validation is required to confirm the predicted targets and elucidate their roles in these processes. The differential expression of miRNAs in response to LDL and latex particles highlights their potential regulatory roles in cellular processes. Understanding these mechanisms could provide new insights into the molecular basis of lipid metabolism and inflammation in various cell types.
Funding Source: This work was supported by the Russian Science Foundation (Grant No. 22-65-00089)