miR‑24 regulates angiogenesis in gliomas

Abstract

Gliomas are one of the most common and most aggressive types of central nervous system tumor. Angiogenesis is an important basis for the growth of solid tumors, including gliomas, which is regulated by microRNAs (miRNAs). However, the mechanism remains unclear. Recently, it was demonstrated that miR‑24 was upregulated in gliomas, so the aim of the present study is to establish whether the dysregulation of miR‑24 in glioma cells promotes microvascular proliferation of endothelial cells (ECs), and to investigate the potential mechanism. miR‑24 was overexpressed or downregulated in U251 glioma cell line cells using miR‑24 mimics or inhibitors, respectively. Subsequently, the effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on cell viability, migration and angiogenesis of human umbilical vein ECs (HUVECs) were examined. The expression levels of vascular endothelial growth factor (VEGF) mRNA, basic fibroblast growth factor (bFGF) mRNA, epidermal growth factor (EGF) mRNA, transforming growth factor (TGF)‑β mRNA, matrix metalloproteinase (MMP)‑2 mRNA and MMP‑9 mRNA, and the mRNA and protein levels of VEGF and TGF‑β in miR‑24 mimic‑ or inhibitor‑transfected U251 cells were obtained by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on expression levels of VEGF mRNA, TGF‑β mRNA, MMP‑2 mRNA and MMP‑9 mRNA, and mRNA and protein expression levels of VEGF and TGF‑β, and intracellular AKT and β‑catenin signaling in HUVECs were also examined. The results indicated that the conditional medium from miR‑24 mimic‑transfected U251 cells exhibited significantly increased cell viability, cell migration and tube formation of HUVECs. By contrast, the conditional medium from miR‑24 inhibitor‑transfected U251 cells exhibited significantly decreased cell viability, cell migration and tube formation of HUVECs. Enforced expression of miR‑24 in U251 cells may promote the cell viability and angiogenesis of HUVECs. The mRNA expression levels of VEGF, bFGF, EGF, TGF‑β, MMP‑2 and MMP‑9 in U251 cells were significantly increased by miR‑24 mimics. Western blot detection confirmed the increased levels of VEGF and TGF‑β protein expression in U251 by miR‑24 mimics, and the decrease of VEGF and TGF‑β protein expression levels in U251 by miR‑24 inhibitors. The conditional medium from miR‑24 mimic‑transfected U251 cells increased the expression levels of the angiogenesis‑associated factors, including VEGF, TGF‑β, MMP‑2, and MMP‑9. By contrast, reduced expression of miR‑24 in U251 cells may downregulate the expression of those angiogenesis‑associated factors. Thus, miR‑24 in U251 cells may be important in the angiogenesis of HUVECs via VEGF and TGF‑β, and the intracellular signaling of AKT and β‑catenin may be involved in this process.

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

“…Since most of the findings were obtained using exogenously expressed miRNAs, further studies are required to evaluate the translational potential of our results. Nonetheless, our findings are consistent with the observation of miR-24 expression in endothelial cells [42][43][44]87] and its roles as a regulator of various cerebrovascular phenomena, including angiogenesis in gliomas [88,89] and vasospasm following subarachnoid hemorrhage [90]. The study also has some strengths, including the fact that the 3 -UTR of Neuropilin-1 that is targeted by miR-24 is highly conserved among species, from primates to rodents.…”

miR-24 targets SARS-CoV-2 co-factor Neuropilin-1 in human brain microvascular endothelial cells: Insights for COVID-19 neurological manifestations

“…Since most of the ndings were obtained using exogenously expressed miRNAs, further studies are required to evaluate the translational potential of our results. Nonetheless, our ndings are consistent with the observation of miR-24 expression in endothelial cells [42][43][44]87] and its roles as a regulator of various cerebrovascular phenomena, including angiogenesis in gliomas [88,89] and vasospasm following subarachnoid hemorrhage [90]. The study also has some strengths, including the fact that the 3′-UTR of Neuropilin-1 that is targeted by miR-24 is highly conserved among species, from primates to rodents.…”

Decreased expression of miR‐24 in peripheral plasma of type 2 diabetes mellitus patients associated with diabetic foot ulcer

“…In addition, it has been found that the change of miR‐24 expression in fibroblasts could affect the aging and functional state of fibroblasts by modifying the activity of DNA topoisomerase I, 33 and also affect the proliferation activity of fibroblasts by regulating the expression of cell cycle regulatory genes 34 . In terms of the influence on angiogenesis, it has been revealed that miR‐24 could regulate the expression of VEGF and TGF‐β in HUVECs cells through the signal pathway of Akt and β‐Catenin, and then participate in angiogenesis 35 . In addition, another study found that the down‐regulation of miR‐24 expression in high glucose environment could affect the proliferation, migration, differentiation and angiogenesis of vascular endothelial cells by targeting the transcription factor PATZ1 36 .…”