Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?

Kwong, Francois Ng Kee; Nicholson, Andrew G.; Harrison, Celeste L.; Hansbro, Philip M.; Adcock, Ian M.; Chung, Kian Fan

doi:10.1183/16000617.0040-2017

Cited by 43 publications

(23 citation statements)

References 128 publications

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“…The stressors leading to senescence include telomere shortening due to replicative exhaustion, DNA or chromatin structure and mitochondrial dysfunction [15][16][17][18][19]. Recent reports indicated that mitochondrial dysfunction plays an important role in initiating inflammatory responses and cellular senescence and has significance in the pathogenesis of lung disease [20].…”

Section: Discussionmentioning

confidence: 99%

miR-200b regulates cellular senescence and inflammatory responses by targeting ZEB2 in pulmonary emphysema

Shen

Xuan

Wang

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Smoking is an important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), which is commonly characterised by cellular senescence and inflammation. Recently, miR-200b has emerged as an important target to cure lung disease; however, the function of miR-200b in reducing cellular senescence and inflammatory responses has not been reported. In this study, we found that miR-200b was downregulated in the lungs of COPD model mice, and its expression is correlated with cellular senescence and inflammatory responses. We hypothesised that miR-200b may be a potential novel therapy for treating COPD. We performed senescence-Associated-b-galactosidase (SA-b-GAL) staining, western blot, qRT-PCR and ELISA; our data suggested that miR-200b is an anti-aging factor in the lungs that is involved in inflammatory responses. We also confirmed that ZEB2 (Zinc finger E-box binding homeobox 2) is a target gene of miR-200b using luciferase reporter assay. In addition, we verified the function of ZEB2 in cellular senescence and inflammatory responses through transfection experiments. Moreover, we found that the protective effects of miR-200b are inhibited when cells overexpress the ZEB2 protein. In conclusion, our results suggest that miR-200b may attenuate cellular senescence and inflammatory responses by targeting ZEB2 in pulmonary emphysema.

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Section: Discussionmentioning

confidence: 99%

miR-200b regulates cellular senescence and inflammatory responses by targeting ZEB2 in pulmonary emphysema

Shen

Xuan

Wang

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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“…Roles for urokinase plasminogen activation receptor (uPAR) in modulating EMT and direct associations between uPAR and vimentin expression in were also suggested (37). Mitochondrial dysfunction can also lead to EMT in smokers and COPD, hence cancer (38).…”

Section: Emt In Copdmentioning

confidence: 99%

Heparin-binding epidermal growth factor (HB-EGF) drives EMT in patients with COPD: implications for disease pathogenesis and novel therapies

Eapen

Sharma

Thompson

et al. 2019

Laboratory Investigation

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Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation. Small airway fibrosis and obliteration are known to cause fixed airflow obstruction in COPD, and the consequential damage to the lung has an early onset. So far, there is little evidence of the mechanisms that underlie this aspect of pathology. However, emerging research confirms that airway epithelial reprogramming or epithelial to mesenchymal transition (EMT) is a key mechanism that drives fibrotic remodelling changes in smokers and patients with COPD. A recent study by Lai et al, further highlights the importance of EMT in smoking-related COPD pathology. The authors identify HB-EGF, an EGFR ligand, as a key driver of EMT and a potential new therapeutic target for the amelioration of EMT and airway remodelling. There are also wider implications in lung cancer prophylaxis, which is another major comorbidity associated with COPD. We consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications.

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“…In general, autophagy is regarded as a safety mechanism counteracting hyperactivation of inflammasomes and chronic inflammation-induced cancer [12]. Defects in canonical autophagy or mitophagy can lead to pathological responses and necrosis, promoting chronic inflammation and tumorigenesis [12,13]. Additionally, autophagy levels have been associated with cell death fate and cell clearance [12].…”

Section: Introductionmentioning

confidence: 99%

Crosstalks between inflammasome and autophagy in cancer

et al. 2020

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Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anticancer strategies, although it remains underexplored in terms of their crosstalks.

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Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?

Cited by 43 publications

References 128 publications

miR-200b regulates cellular senescence and inflammatory responses by targeting ZEB2 in pulmonary emphysema

miR-200b regulates cellular senescence and inflammatory responses by targeting ZEB2 in pulmonary emphysema

Heparin-binding epidermal growth factor (HB-EGF) drives EMT in patients with COPD: implications for disease pathogenesis and novel therapies

Crosstalks between inflammasome and autophagy in cancer

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