miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis
AbstractSeveral 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 3′untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF. View Full-Text
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Zhang, S.; Liu, H.; Liu, Y.; Zhang, J.; Li, H.; Liu, W.; Cao, G.; Xv, P.; Zhang, J.; Lv, C.; Song, X. miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci. 2017, 18, 633.
Zhang S, Liu H, Liu Y, Zhang J, Li H, Liu W, Cao G, Xv P, Zhang J, Lv C, Song X. miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis. International Journal of Molecular Sciences. 2017; 18(3):633.Chicago/Turabian Style
Zhang, Songzi; Liu, Huizhu; Liu, Yuxia; Zhang, Jie; Li, Hongbo; Liu, Weili; Cao, Guohong; Xv, Pan; Zhang, Jinjin; Lv, Changjun; Song, Xiaodong. 2017. "miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis." Int. J. Mol. Sci. 18, no. 3: 633.
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