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- Title
miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis.
- Authors
Songzi Zhang; Huizhu Liu; Yuxia Liu; Jie Zhang; Hongbo Li; Weili Liu; Guohong Cao; Pan Xv; Jinjin Zhang; Changjun Lv; Xiaodong Song
- Abstract
Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in idiopathic pulmonary fibrosis (IPF) regulation is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 is yet to be investigated. Additionally, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual-luciferase reporter assay system were used to identify the target gene of miR-30a, and cell transfection was utilized to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and miR-30a mimic and inhibitor transfection significantly reduced and increased the TET1 protein expression, respectively. Further experimentation verified that the TET1 siRNA interference could inhibit Drp-1 promoter hydroxymethylation. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 30untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF.
- Subjects
MICRORNA; IDIOPATHIC pulmonary fibrosis; CHROMOSOMAL translocation; EPITHELIAL cells; DYNAMIN (Genetics); THERAPEUTICS
- Publication
International Journal of Molecular Sciences, 2017, Vol 18, Issue 3, p633
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms18030633