Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug

• Published in: International journal of molecular sciences 2021-10, Vol.22 (21), p.11309
• Main Authors: Liang, Xinxin, Yan, Ziyan, Wang, Ping, Liu, Yuhao, Ao, Xingkun, Liu, Zheng, Wang, Duo, Liu, Xiaochang, Zhu, Maoxiang, Gao, Shanshan, Xie, Dafei, Zhou, Pingkun, Gu, Yongqing
• Format: Article
• Language: English
• Subjects: A549 Cells; Alveolar Epithelial Cells - metabolism; Alveoli; Animals; Binding sites; Cell Line, Tumor; Datasets; EMT; Epithelial cells; Epithelial-Mesenchymal Transition - genetics; Epithelial-Mesenchymal Transition - radiation effects; Epithelium; Fibroblasts; Fibrosis; Gene expression; Humans; Kinases; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Lung - metabolism; Lung - physiology; Lung diseases; Lung Injury - physiopathology; Lymphoma; Male; Mesenchyme; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-541-5p; MZF1; Online data bases; Plasmids; Prostate cancer; Protein expression; Proteins; Pulmonary fibrosis; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Radiation; Radiation effects; Radiation Fibrosis Syndrome - genetics; radiation-induced pulmonary fibrosis; Signal Transduction - physiology; slug; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Therapeutic applications; Transcription factors; Transcription Factors - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111309

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 ( ) 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 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting . Thus, irradiation activates to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting . Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.