title: miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis.
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 3'untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF.
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. 13954359981@163.com.|Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Taishan Medical University, Taishan 271016, China. 13954359981@163.com.
authors.forename: Songzi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. 18865675850@163.com.
authors.forename: Huizhu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. yimeng3183@163.com.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. 18547131029@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. lihongbo0516@sina.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. lwl249880849@163.com.
authors.forename: Weili
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. cgh861025@126.com.
authors.forename: Guohong
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. xupan_333@126.com.
authors.forename: Pan
authors.initials: P
authors.lastname: Xv
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. jjinzhang@126.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. lucky_lcj@sina.com.|Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. lucky_lcj@sina.com.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. songxd71@163.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D064550:Death-Associated Protein Kinases
keywords: Drp-1; TET1; idiopathic pulmonary fibrosis; miR-30a