MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells

Abstract

MicroRNA-125a-5p (miR-125a-5p) could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low-density lipoprotein (ox-LDL)-induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis, and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway and phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt)/endothelial nitric oxide synthase (eNOS) pathway were analyzed. Results showed the following: ) Expression of miR-125a-5p was reduced in ox-LDL-treated HBMEC.) Overexpression of miR-125a-5p protected HBMEC from ox-LDL-induced apoptosis, senescence, ROS production, and NO reduction. ) Overexpression of miR-125a-5p increased HBMEC proliferation, migration, and tube formation, while decreasing HBMEC adhesion to leukocytes, as well as counteracting the effects of ox-LDL on those functions.) The levels of EGFR/ERK/p38 MAPK pathway, PI3K/Akt/eNOS pathway, cleaved caspase-3, and adherent molecular ICAM-1 and VCAM-1 were associated with the effects of ox-LDL on these HBMEC functions. In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression.

MicroRNA-125a Regulates Cell Proliferation Via Directly Targeting E2F2 in Osteosarcoma

“…Studies have suggested that miR-125a can inhibit the tumor growth and play a tumor-suppressive role [7-11, 14]. miR-125a has a low expression in a variety of tumors [7-11], but its expression and function in osteosarcoma have not been studied.…”

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

“…In human brain microvessel endothelial cells (HBMECs), ox-LDL reduces the expression of miR-125a, the function of which is to counteract the effects of ox-LDL on inflammation, namely the expression of ICAM-1 and VCAM-1 and leukocyte adhesion. In vitro miR-125a promotes HBMEC proliferation, migration, and tube formation (11). Though the direct targets of miR-125a in HBMECs require further studies, the target of miR-125b in the mouse heart is TRAF6, an adaptor molecule in the NF-kB pathway.…”

MicroRNA Regulation of Oxidative Stress‐Induced Cellular Senescence

“…Overexpression of these miRNAs altogether increased cellular senescence and ROS production, which could be antagonized by CKII overexpression [128]. miR-125a-5p was downregulated in human brain microvessel endothelial cells by ox-LDL, a risk factor for vascular diseases by inducing proinflammatory and proatherogenic responses [129]. Overexpression of this miRNA increased nitric oxide production and decreased ROS production, consequently reducing senescence and apoptosis.…”

“…Overexpression of this miRNA increased nitric oxide production and decreased ROS production, consequently reducing senescence and apoptosis. miR-125a-5p also improved endothelial cell function and decreased cell adhesion to leukocytes, indicating an anti-inflammatory role by decreasing leukocyte recruitment [129]. …”