MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Gokey, Jason J.; Snowball, John; Sridharan, Anusha; Speth, Joseph P; Black, Katharine E.; Hariri, Lida P.; Perl, Anne‐Karina T.; Xu, Yan; Whitsett, Jeffrey A.

doi:10.1172/jci.insight.122490

Cited by 55 publications

(38 citation statements)

References 68 publications

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“…Additionally, epithelial MEG3 expression has been shown to be induced by cigarette smoke, correlate with disease severity, and promote inflammation and apoptosis through a mechanism involving miR-218 ( 186 ). MEG3 expression is also increased in atypical IPF epithelial cells and can impair basal cell differentiation, which may contribute to abnormal tissue remodeling ( 105 ). Notably, p53 can induce both cellular senescence and apoptosis in a context-dependent manner, but the role of lincRNA-p21 and MEG3 in regulating p53-mediated cell fate responses in the lung remain unknown.…”

Section: Non-coding Rnas In Aging Ipf and Copdmentioning

confidence: 99%

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Omote

Sauler

2020

Front. Med.

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Cellular senescence is a cell fate implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Cellular senescence occurs in response to cellular stressors such as oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction. Whether these stresses induce cellular senescence or an alternative cell fate depends on the type and magnitude of cellular stress, but also on intrinsic factors regulating the cellular stress response. Non-coding RNAs, including both microRNAs and long non-coding RNAs, are key regulators of cellular stress responses and susceptibility to cellular senescence. In this review, we will discuss cellular mechanisms that contribute to senescence in IPF and COPD and highlight recent advances in our understanding of how these processes are influenced by non-coding RNAs. We will also discuss the potential therapeutic role for targeting non-coding RNAs to treat these chronic lung diseases.

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Section: Non-coding Rnas In Aging Ipf and Copdmentioning

confidence: 99%

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Omote

Sauler

2020

Front. Med.

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“…The unconfirmed lncRNAs present novel potential lncRNAs that could be further studied as regulatory drivers of the disease, clinical biomarkers, and therapeutic targets. MEG3, a top lncRNA for both COPD and RTIs, is differentially expressed in pulmonary fibrosis and in COPD (Tang et al, 2016; Gokey et al, 2018), indicating it may play a key role in the pathology of multiple respiratory diseases. IFNG-AS1, a top lncRNA for only RTIs but not COPD, has been linked to T helper cell responses (Peng et al, 2015), suggesting it may play a role in the immune response component of RTIs.…”

Section: Resultsmentioning

confidence: 99%

Network Diffusion Approach to Predict LncRNA Disease Associations Using Multi-Type Biological Networks: LION

et al. 2019

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Recently, long-non-coding RNAs (lncRNAs) have attracted attention because of their emerging role in many important biological mechanisms. The accumulating evidence indicates that the dysregulation of lncRNAs is associated with complex diseases. However, only a few lncRNA-disease associations have been experimentally validated and therefore, predicting potential lncRNAs that are associated with diseases become an important task. Current computational approaches often use known lncRNA-disease associations to predict potential lncRNA-disease links. In this work, we exploited the topology of multi-level networks to propose the L ncRNA rank I ng by Netw O rk Diffusio N (LION) approach to identify lncRNA-disease associations. The multi-level complex network consisted of lncRNA-protein, protein–protein interactions, and protein-disease associations. We applied the network diffusion algorithm of LION to predict the lncRNA-disease associations within the multi-level network. LION achieved an AUC value of 96.8% for cardiovascular diseases, 91.9% for cancer, and 90.2% for neurological diseases by using experimentally verified lncRNAs associated with diseases. Furthermore, compared to a similar approach (TPGLDA), LION performed better for cardiovascular diseases and cancer. Given the versatile role played by lncRNAs in different biological mechanisms that are perturbed in diseases, LION’s accurate prediction of lncRNA-disease associations helps in ranking lncRNAs that could function as potential biomarkers and potential drug targets.

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“…3h, Supplementary Figure 3e). Meg3 is a known regulator of epithelial cell differentiation, while Abca3 is a crucial factor in surfactant and lamellar bodies' metabolism 11,12 . Mutations of Abca3 have been associated with interstitial lung disease and progressive respiratory distress syndrome and further, knock-down of Abca3 resulted in abnormal lamellar bodies 13 .…”

Section: Hyperoxia Alters At2 Cells Population In Developing Lungsmentioning

confidence: 99%

Multiplexed single-cell transcriptomic analysis of normal and impaired lung development in the mouse

Hurskainen

Mižíková

Cook

et al. 2019

Preprint

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During late lung development alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia. We observed dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, capillary endothelium and macrophage populations. We identified several BPD-associated signatures, including Pdgfra in fibroblasts, Activin A in capillary endothelial cells, and Csf1-Csf1r and Ccl2-Ccr2 signaling in macrophages and neutrophils. Our data provides a novel single-cell view of cellular changes associated with late lung development in health and in disease.

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MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Cited by 55 publications

References 68 publications

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

Network Diffusion Approach to Predict LncRNA Disease Associations Using Multi-Type Biological Networks: LION

Multiplexed single-cell transcriptomic analysis of normal and impaired lung development in the mouse

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