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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473730.do
DOI
10.1038/cddis.2017.219
Title
A miRNA-101-3p/Bim axis as a determinant of serum deprivation-inducedendothelial cell apoptosis
Description
This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIP) (2013M3A9B6046367 and2016M3A9B6903103).
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.
provenance
Made available in Cube on 2018-09-28T10:27:21Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Ji-Hee
Lee, Dong-Keon
Kim, Joohwan
Choi, Seunghwan
Park, Wonjin
Ha, Kwon-Soo
Kim, Tae-Hoon
Choe, Jongseon
Won, Moo-Ho
Kwon, Young-Guen
Kim, Young-Myeong
accessioned
2018-09-28T10:27:21Z
available
2018-09-28T10:27:21Z
issued
2017
citation
CELL DEATH & DISEASE(8)
issn
2041-4889
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473730.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274450
Jurisdiction
Rep.of Korea
Project Name
Professional Education Initiative for Medical Innovation with BIT Convergence
rights
openAccess
type
article


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