Long non‑coding RNA HOTTIP enhances the fibrosis of lung tissues by regulating the miR‑744‑5p/PTBP1 signaling axis

Li,Jing; Chai,Wenshu; Zhao,Zhuo; Zhou,Yan; Wu,Qi

doi:10.3892/mmr.2021.12258

Long non‑coding RNA HOTTIP enhances the fibrosis of lung tissues by regulating the miR‑744‑5p/PTBP1 signaling axis

Authors:
- Jing Li
- Wenshu Chai
- Zhuo Zhao
- Yan Zhou
- Qi Wu
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Affiliations: Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Respiratory Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Intensive Care Unit Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: June 30, 2021 https://doi.org/10.3892/mmr.2021.12258
Article Number: 619
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fibrosis of lung tissue can induce the occurrence and development of numerous types of lung disease. The expression levels of the long non‑coding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) have been reported to be upregulated during the development of fibrosis in liver tissues, which subsequently activated hepatic stellate cells. However, whether the lncRNA HOTTIP participates in the occurrence and development of lung fibrosis remains unknown. The present study aimed to investigate the role of lncRNA HOTTIP in lung fibrosis and its potential mechanism. In the present study, A549 cells were stimulated with TGF‑β1 to induce lung fibrosis in vitro. A549 was transfected with short hairpin RNA‑HOTTP, overexpression‑polypyrimidine tract binding protein 1 (PTBP1), microRNA (miR)‑744‑5p mimic or miR‑744‑5p to regulate gene expression. Cell proliferation and migration were determined using 5'‑ethynl‑2'‑deoxyuridine and wound healing assays, respectively. The expression levels of α‑smooth muscle actin, collagen I, collagen III and fibronectin 1 were analyzed using western blotting. starBase was used to identify molecules that may interact with the lncRNA HOTTIP and dual luciferase reporter assays were used to validate the findings. Moreover, an in vivo lung fibrosis model was established by bleomycin induction in mice. Histological injury was observed using hematoxylin and eosin and masson staining. The results of the present study revealed that the proliferation and migration of A549 cells were both suppressed following the knockdown of HOTTIP. The lncRNA HOTTIP was found to target and downregulate the expression levels of miR‑744‑5p. The overexpression of miR‑744‑5p inhibited the proliferation and migration of A549 cells. Furthermore, miR‑744‑5p targeted and downregulated the expression levels of PTBP1. It was subsequently demonstrated that the overexpression of PTBP1 rescued miR‑744‑5p‑induced suppression of the proliferation and migration of A549 cells. The knockdown of lncRNA HOTTIP expression also relieved the fibrosis of the lung tissues of mice. In conclusion, the results of the present study suggested that the lncRNA HOTTIP may promote the fibrosis of lung tissues by downregulating the expression levels of miR‑744‑5p and upregulating the expression levels of PTBP1.

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