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

Ji Hee Kim, Dong Keon Lee, Joohwan Kim, Seunghwan Choi, Wonjin Park, Kwon Soo Ha, Tae Hoon Kim, Jongseon Choe, Moo Ho Won, Young Guen Kwon, Young Myeong Kim

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26 Citations (Scopus)


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.

Original languageEnglish
Article numbere2808
JournalCell Death and Disease
Issue number5
Publication statusPublished - 2017

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2013M3A9B6046367 and 2016M3A9B6903103).

Publisher Copyright:
© The Author(s) 2017.

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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