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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.

SUBMITTER: Kim JH

PROVIDER: S-EPMC5520733 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Kim Ji-Hee JH Lee Dong-Keon DK Kim Joohwan J Choi Seunghwan S Park Wonjin W Ha Kwon-Soo KS Kim Tae-Hoon TH Choe Jongseon J Won Moo-Ho MH Kwon Young-Guen YG Kim Young-Myeong YM

Cell death & disease 20170518 5

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 s ...[more]

PMID: 28518140

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Dataset Information

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

Publications

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

Similar Datasets

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