Knockdown of long non‑coding RNA DLEU2 suppresses idiopathic pulmonary fibrosis by regulating the microRNA‑369‑3p/TRIM2 axis

Yi,Hengzhong; Luo,Danlin; Xiao,Yangbao; Jiang,Di

doi:10.3892/ijmm.2021.4913

Knockdown of long non‑coding RNA DLEU2 suppresses idiopathic pulmonary fibrosis by regulating the microRNA‑369‑3p/TRIM2 axis

Authors:
- Hengzhong Yi
- Danlin Luo
- Yangbao Xiao
- Di Jiang
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Affiliations: Sixth Medical Department, Hunan Chest Hospital, Changsha, Hunan 410013, P.R. China, Endoscopy Center, Hunan Chest Hospital, Changsha, Hunan 410013, P.R. China, Department of Ultrasound, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: March 11, 2021 https://doi.org/10.3892/ijmm.2021.4913
Article Number: 80
Copyright: © Yi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia with an increasing incidence. In the present study, Genome Expression Omnibus (GEO) datasets (GSE10667, GSE24206 and GSE32537) were applied to identify lncRNA DLEU2 in IPF. Through prediction using starBase, TargetScan, miRTarBase and miRDB, tripartite motif containing 2 (TRIM2) and prostaglandin F2 receptor inhibitor (PTGFRN) were found to be upregulated in IPF. DLEU2 expression, the mRNA expression of TRIM2 and PTGFRN, and miR‑369‑3p expression in A549 cells and lung tissues were detected by RT‑qPCR. The protein expression of TRIM2 and PTGFRN in lung tissues and A549 cells was detected by western blot analysis. The proliferation and migration of A549 cells was respectively detected by CCK‑8 assay and wound healing assay. The expression of collagen I, α‑smooth muscle actin (SMA) and E‑cadherin was detected by immunofluorescence assay in A549 cells, and collagen I expression was detected by immunohistochemistry assay in lung tissues. The expression of collagen I, α‑SMA and E‑cadherin was also detected by western blot analysis in A549 cells and lung tissues. Dual‑luciferase reporter assay was used to confirm the association between DLEU2 and miR‑369‑3p, and miR‑369‑3p and TRIM2. As a result, DLEU2 expression was found to be upregulated in IPF and in transforming growth factor (TGF)‑β1‑stimulated A549 cells. The silencing of DLEU2 inhibited the TGF‑β1‑induced proliferation, migration and epithelial‑mesenchymal transition (EMT) of A549 cells and bleomycin (BLM)‑induced pulmonary fibrosis in mice. TRIM2 expression was increased and miR‑369‑3p expression was decreased in the lung tissues of mice with BLM‑induced fibrosis and in TGF‑β1‑stimulated A549 cells. DLEU2 directly targeted miR‑369‑3p. The effect of the silencing of DLEU2 on TGF‑β1‑stimulated A549 cells was suppressed by the silencing of miR‑369‑3p. TRIM2 was the target protein of miR‑369‑3p. On the whole, the present study demonstrates that the silencing of DLEU2 suppressed IPF by upregulating miR‑369‑3p expression and downregulating TRIM2 expression.

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