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.

Interaction network of coexpressed mRNA, miRNA, and lncRNA activated by TGF-β1 regulates EMT in human pulmonary epithelial cell

“…All results are in agreement with those in A549 cell models ( 12 ). As expected, we also identified previously discovered fibrotic miR-30a ( 28 , 29 ), thus validating our microarray data.…”

Downregulation of microRNA‑30a in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis patients

“…Of these 69 miRs there was a greater than 2-fold increase in the expression level of miR-125b-5p, miR-128-3p, miR-21-5p, miR-100-5p, miR-140-3p and miR-374b-5p, and a greater than 2-fold decrease in let-7d, miR-103-3p, miR-30a-5p and miR-27b-3p. The majority of miRs with significant expression differences have been previously reported as potential regulators and biomarkers in IPF progression or IPF-associated carcinogenesis (16)(17)(18)(19)(20)(21)(22)(23), among which miR-30a-5p demonstrated the most significance and was selected for further investigation in the present study (P<0.001).…”

miR-1285-3p Controls Colorectal Cancer Proliferation and Escape from Apoptosis through DAPK2

“…Moreover, DAPK2 is regulated at the transcriptional level by recruitment of several transcription factors to its promoter, such as Sp1, E2F1, KLF6 [39] and the myeloid master regulators PU.1 and C/EBPα [40]. Post-transcriptional regulation of DAPK2 expression by non-coding RNAs (ncRNAs) has been reported in the recent literature [41][42][43]. Here, we demonstrate that DAPK2 expression in colorectal cancer is controlled by miR-1285, thus providing further insight into the post-transcriptional layer of DAPK2 regulation.…”