Abstract
Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
Highlights
Would help establish new avenues for further uncovering the mechanisms underlying radiationinduced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets
The results revealed the role of the transcription factor MZF1 (Myeloid Zinc Finger 1), which has been previously reported to be an important transcriptional repressor
Since MZF1 could inhibit miR-541-5p, which could target Slug, we explored what happens to epithelial-mesenchymal transition (EMT)-associated proteins when MZF1 is overexpressed, and Slug is knocked down
Summary
Would help establish new avenues for further uncovering the mechanisms underlying radiationinduced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiationinduced-EMT in vitro and in vivo. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR541-5p expression mitigated RIPF in mice by targeting Slug. Irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. MiR-541-5p was found down-regulated in the radiation-induced pulmonary fibrosis model.
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