LncRNA TUG1 promotes pulmonary fibrosis progression via up-regulating CDC27 and activating PI3K/Akt/mTOR pathway

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with an unclear pathogenesis. This study aimed to elucidate the function and potential mechanisms of TUG1 in IPF progression. Cell viability and migration were detected by CCK-8 and transwell assays. Autophagy, fibrosis, or EMT-related proteins were measured by Western blotting. Pro-inflammatory cytokine levels were assessed by ELISA kits. The subcellular localization of TUG1 was observed by FISH assay. RIP assay detected the interaction between TUG1 and CDC27. TUG1 and CDC27 was up-regulated in TGF-β1-induced RLE-6TN cells. TUG1 depletion suppressed pulmonary fibrosis via attenuating inflammation, EMT, inducing autophagy and inactivating PI3K/Akt/mTOR pathway in vitro and in vivo. TUG1 knockdown prevented CDC27 expression. TUG1 silencing ameliorated pulmonary fibrosis by reducing CDC27 expression and inhibiting PI3K/Akt/mTOR pathway.

The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets

“…Although TUG1 has 20 transcripts, 19 of them do not have the ability to encode proteins ( Farzaneh et al, 2022 ). Previous studies have shown that TUG1 played an oncogenic role in tumors such as colorectal ( Ibrahim et al, 2023 ), prostate ( Yu et al, 2019 ), bladder ( Tan et al, 2022 ), lung ( Li et al, 2021a ), oral squamous cell ( Jiang et al, 2022 ), and ovarian cancers ( Zhan et al, 2020 ), as well as being involved in the pathogenesis of non-cancerous diseases such as renal ischemia-reperfusion injury ( Sun et al, 2022b ), pulmonary fibrosis ( Qi et al, 2023 ), and myocardial infarction ( Dang et al, 2023 ). Thus, TUG1 could act as a pathogenic factor in a tissue-specific or environment-specific manner.…”

TRIM2, S100A14, CYP4B1, LMO7, and SFN are signature genes in the progression of idiopathic pulmonary fibrosis epithelial cells to their lung adenocarcinoma comorbidities: a comprehensive analysis based on single-cell RNA sequencing data and RNA transcriptome data

“…Activation of the PI3K-Akt signaling pathway has been reported to be closely related to IPF progression: up-regulation of the PI3K p110 heterodimer is associated with the overexpression of α-SMA in IPF fibroblasts and activation of phosphorylated Akt is also involved in fibrotic progression in IPF [31,32]. Fei Qi et al found that lncRNA TUG1 induced autophagy and suppressed inflammation and EMT through inhibition of the PI3K/Akt/mTOR signaling pathway, resulting in an improved pulmonary fibrosis phenotype [33]. Xiaohe Li et al obtained similar outcomes that Duvelisib silenced the expression of fibroblasts in the lungs of patients with IPF and activated autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway [34].…”

Anti-Inflammatory and Antifibrotic Potential of Longidaze in Bleomycin-Induced Pulmonary Fibrosis

“…Levels of the profibrotic cytokine TGF-β directly correlate with the Life 2023, 13,1932 2 of 21 severity of IPF disease [7,8]. TGF-β is believed to induce epithelial-mesenchymal transition and differentiation of fibroblasts into myofibroblasts, which contribute to the excessive synthesis and deposition of ECM proteins in the lung [9,10]. In addition, the concentration of hyaluronic acid (HA), a key component of the ECM, increases in the lung in IPF [11,12].…”

“…The pathogenesis of pulmonary fibrosis is complex and not fully understood, which hinders the development of specific therapies. Current treatment options for IPF remain limited [ 8 , 10 ]. Pirfenidone axunio and Nintedanib esilat, known on the pharmaceutical market for the treatment of IPF, have not shown the expected high antifibrotic activity; they can only slow down the progression of the disease, and due to the risk of serious side effects, their use is limited [ 16 ].…”