Dataset Information

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

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.

SUBMITTER: Liang X

PROVIDER: S-EPMC8582843 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Purpose: Genistein is a natural phytoestrogen with various antitumor effects. In recent years, some microRNAs (miRNA) in cancer cells have been reported to be regulated by genistein. Our study focused on exploring the mechanisms of miRNA upregulation to inhibit the epithelial mesenchymal transformation (EMT) and stemness of hepatocellular carcinoma (HCC). Patients and Methods: MiR-1275 was discovered by the transcriptome sequencing of miRNA expression profiles in HepG2 cells treated with genistein or DMSO as a control. Then, we performed series functional experiments in vitro and vivo to explore the relationship between genistein and miR-1275 in HCC. The target gene (Eukaryotic initiation factor 5A2, EIF5A2) of miR-1275 was predicted by databases and finally determined by a dual luciferase reporter assay. The downstream signaling pathway of EIF5A2 was assessed by bioinformatics analysis and Western blot. Results: the inhibition of genistein on the viability of HCC cells was enhanced by the increase in treatment time and dose, but it had no obvious inhibitory effect on normal hepatocytes (QSG-7701). Through qRT-PCR and transcriptome sequencing, we discovered that miR-1275 was lowly expressed in HCC, and it can be raised by genistein. The overall survival (OS) and recurrence-free survival (RFS) of HCC patients with lowly expressed miR-1275 were lower than those of those with high expression levels. In vitro and vivo experiments exhibited that genistein and the overexpression of miR-1275 can both significantly suppress the proliferation, migration, invasion, metastasis, EMT and stemness of HCC. Moreover, the inhibition can be further enhanced when miR-1275 mimic and genistein exist together. Finally, we demonstrated that miR-1275 can inhibit the epithelial mesenchymal transformation (EMT) and stemness of HCC via inhibiting the EIF5A2/PI3K/Akt pathway. Conclusion: Our findings proved that genistein can inhibit the EIF5A2/PI3K/Akt pathway by upregulating miR-1275 so as to attenuate the EMT and stemness of HCC cells to restrict their progression and metastasis.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets