A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis

Abstract

Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3′-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3′-untranslated region (3′-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.

miRNA‑101‑3p.1 as an independent diagnostic biomarker aggravates chronic obstructive pulmonary disease via activation of the EGFR/PI3K/AKT signaling pathway

“…clinical and pathological studies indicated that overexpression of inflammatory cytokines can cause histopathological injury and inhibit the proliferation of airway cells, causing airway reconstruction and pulmonary function decline (34,35). The present results demonstrated that increasing mirna-101-3p.1 promoted PBMC proliferation, a finding largely consistent with a study by Kim et al (36) in which mir-101-3p played an important role in promoting proliferation and inhibiting endothelial cell apoptosis. increased PBMc proliferation promotes the infiltration of large numbers of mononuclear cells in the lung.…”

miR-5591-5p regulates the effect of ADSCs in repairing diabetic wound via targeting AGEs/AGER/JNK signaling axis

“…Because miRNAs have been reported to regulate intracellular ROS production and apoptosis signaling in endothelial cells during diabetes 20 , 21 , we used a miRNA array to analyze the miRNA profiles in AGEs-treated ADSCs and control cells. The data showed a large number of miRNAs that were downregulated in AGEs-treated ADSCs (Fig.…”

High PGAM5 expression induces chemoresistance by enhancing Bcl-xL-mediated anti-apoptotic signaling and predicts poor prognosis in hepatocellular carcinoma patients

“…Immunoprecipitation was done by following the procedure described in earlier studies 30 . Cells (2 × 10 7 ) were lysated and sonicated in a cell lysis buffer (20 mM Tris (pH 7.5), 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1% Triton X-100, 2.5 mM sodium pyrophosphate, 10 mg/ml protease inhibitor cocktail) on ice.…”