The transcription factor c-Myc suppresses MiR-23b and MiR-27b transcription during fetal distress and increases the sensitivity of neurons to hypoxia-induced apoptosis

PloS One
Qun ChenQipeng Zhang

Abstract

Previous studies reported that the expression of miR-23b-27b cluster was downregulated in embryonic brain cortices during hypoxia-induced neuronal apoptosis. However, the mechanism underlying this downregulation is not completely understood. Here, we report that the transcription factor c-Myc plays an important role in regulating the expression of miR-23b-27b cluster during hypoxia. First, the c-Myc protein level was significantly elevated in embryonic brain cortices in a mouse model of fetal distress. Second, forced overexpression or knockdown of c-Myc could suppress or increase the expression of miR-23b-27b cluster polynucleotides. Third, we identified 2 conserved c-Myc binding sites (E-boxes) in the enhancer and promoter regions of miR-23b-27b cluster in the mouse genome. Finally, we showed that elevated c-Myc expression led to an increase in the Apaf-1 level by suppressing miR-23b-27b cluster expression and that this enhanced neuronal sensitivity to apoptosis. In summary, our study demonstrates that c-Myc may suppress the expression of the miR-23b-27b cluster, resulting in additional neuronal apoptosis during hypoxia.

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Citations

Feb 20, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ankita SrivastavaAnil Nilkanth Gaikwad
Jan 24, 2018·Journal of Neurotrauma·Bao-Shu XieJi-Yao Jiang
May 3, 2018·Physiological Reviews·Charles A DucsayLubo Zhang
Apr 18, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shuxin LiangYong Zhang
Sep 14, 2019·International Journal of Molecular Sciences·Yang-Hsiang Lin
Dec 5, 2018·Frontiers in Neuroscience·Natalia N NalivaevaIgor A Zhuravin

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Methods Mentioned

BETA
transfection
PCR
immunoprecipitation
ChIP

Software Mentioned

BandScan
Prism

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