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Radiation induced transcriptional and post-transcriptional regulation of the hsa-miR-23a~27a~24-2 cluster suppresses apoptosis by stabilizing XIAP.
Biochim. Biophys. Acta 1860, 1127-1137 (2017)
The non-coding transcriptome, in particular microRNAs (miRNA), influences cellular survival after irradiation. However, the underlying mechanisms of radiation-induced miRNA expression changes and consequently target expression changes are poorly understood. In this study, we show that ionizing radiation decreases expression of the miR-23a~27a~24-2 cluster through transcriptional regulation by promoter methylation and at the post-transcriptional level by reduced processing through AGO-phosphorylation. Furthermore, we demonstrate that all three mature cluster miRNAs reduce apoptosis by increasing expression of the common target protein XIAP. These findings link a temporal succession of transcriptional and post-transcriptional regulatory mechanisms of the miR~23a~24-2~27a cluster, enabling a dynamic stress response and assuring cellular survival after radiation exposure.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Ago ; Methylation ; Phosphorylation ; Promoter ; Stress Response ; Microrna; X-linked Inhibitor; Breast-cancer Cells; Microrna Expression; Argonaute Proteins; Dna Methylation; Ionizing-radiation; Promoter Methylation; Therapeutic Targets; Endothelial-cells; Tumor-suppressor
ISSN (print) / ISBN
0006-3002
Zeitschrift
Biochimica et Biophysica Acta
Quellenangaben
Band: 1860,
Heft: 11,
Seiten: 1127-1137
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
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