LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

Lin, Shupeng; Zhang, Rui; Liu, Xu; Ma, Rui; Xu, Liming; Zhu, Linghua; Hu, Jian; An, Xiuli

doi:10.1038/s41419-020-02889-w

Cited by 42 publications

(24 citation statements)

References 45 publications

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“…However, to validate the effects of RUNX1 inhibition in vitro we used AI-14-91 a validated RUNX1 inhibitor in the HMEC-Ls. Additionally, we have shown that Ro24-7429 causes a reduction in fibrotic makers, a phenotype also reported in studies that inhibited RUNX1 through molecular approaches ( 3 ). We report that RUNX1 localization and signal is increased in a subset of human lungs infected with SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 78%

“…TGF-β1 activation induces extracellular matrix production, and its effects are mediated through the SMAD2/3 pathway as illustrated through SMAD3 knockout that was found to prevent fibrosis in the bleomycin mouse model ( 42 ). Recent publications have highlighted the role of TGF-β1/SMAD/RUNX1 signaling in IPF ( 3 ). There has been growing interest in the role of RUNX1 inhibition in preventing fibrosis in various organ systems including renal tubular epithelial cells in which RUNX1 was found to regulate markers of EMT and knockout of RUNX1 prevented kidney fibrosis ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

“…Pulmonary fibrosis is a chronic and often fatal lung disease characterized by the accumulation of extracellular matrix and the destruction of the lung parenchyma ( 1 , 2 , 3 ) . The cause of pulmonary fibrosis is unknown in most cases, so is termed idiopathic pulmonary fibrosis (IPF).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators

O’Hare

Amarnani

Whitmore

et al. 2021

The American Journal of Pathology

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators

O’Hare

Amarnani

Whitmore

et al. 2021

The American Journal of Pathology

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“…On the other side, RUNX1 modulates the cellular response to TGF-β and promotes myofibroblast differentiation in both marrow-derived and tissue-resident mesenchymal stem cells [ 33 ]. Lin et al [ 34 ] also showed that RUNX1 can promote fibroblast activation and increase α-SMA and fibronectin expression. Additional analysis showed that FER1L4 can induce dysregulation of pathways discovered in TF analysis by acting as ceRNA.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Transcription Factor Activity during Formation of Cancer-Associated Fibroblasts

Kapusta

Dulińska-Litewka

Totoń‐Żurańska

et al. 2020

IJMS

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The reciprocal interactions between cancer cells and the quiescent fibroblasts leading to the activation of cancer-associated fibroblasts (CAFs) serve an important role in cancer progression. Here, we investigated the activation of transcription factors (TFs) in prostate fibroblasts (WPMY cell line) co-cultured with normal prostate or tumorous cells (RWPE1 and RWPE2 cell lines, respectively). After indirect co-cultures, we performed mRNA-seq and predicted TF activity using mRNA expression profiles with the Systems EPigenomics Inference of Regulatory Activity (SEPIRA) package and the GTEx and mRNA-seq data of 483 cultured fibroblasts. The initial differential expression analysis between time points and experimental conditions showed that co-culture with normal epithelial cells mainly promotes an inflammatory response in fibroblasts, whereas with the cancerous epithelial, it stimulates transformation by changing the expression of the genes associated with microfilaments. TF activity analysis revealed only one positively regulated TF in the RWPE1 co-culture alone, while we observed dysregulation of 45 TFs (7 decreased activity and 38 increased activity) uniquely in co-culture with RWPE2. Pathway analysis showed that these 45 dysregulated TFs in fibroblasts co-cultured with RWPE2 cells may be associated with the RUNX1 and PTEN pathways. Moreover, we showed that observed dysregulation could be associated with FER1L4 expression. We conclude that phenotypic changes in fibroblast responses to co-culturing with cancer epithelium result from orchestrated dysregulation of signaling pathways that favor their transformation and motility rather than proinflammatory status. This dysregulation can be observed both at the TF and transcriptome levels.

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“…Persistent in ammation creates a microenvironment that promotes adaptive immunity, proliferation and migration of broblast, secretion of extracellular matrix and deposition of collagen, eventually leading to abnormal lung tissue remodeling and obstructive air exchange, even death [14,15]. The broblast to myo broblast transition is the hallmark of brotic diseases, leading to excessive synthesis and deposition of ECM like Collagen, Fibronectin and Elastin [16,17]. Thus, suppression of EMT process, in ammatory cascade response and broblast activation represents a visible approach for the amelioration of pulmonary brosis.…”

Section: Introductionmentioning

confidence: 99%

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

Cheng

Wang

et al. 2021

Preprint

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Background: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.Methods: The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. SiO2-stimulated lung epithelial cells/macrophages and TGF-β-induced differentiated lung fibroblasts were used for in vitro models.Results: At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2mM to 10mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.Conclusions: In this study, we identified that metformin might be a potential drug for silicosis treatment.

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LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

Cited by 42 publications

References 45 publications

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators

Dysregulation of Transcription Factor Activity during Formation of Cancer-Associated Fibroblasts

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

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