Regulation of human lung alveolar multipotent cells by a novel p38α MAPK/miR-17-92 axis

Oeztuerk-Winder, Feride; Guinot, Anna; Ochałek, Anna; Ventura, Juan-José

doi:10.1038/emboj.2012.192

Cited by 77 publications

(61 citation statements)

References 43 publications

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“…The observed differences in the relative abundance of mature miRNAs from the miR-17~92 cluster by following treatment with miR-92a inhibitor can be attributed to several sources. While mature miRNAs can have half-lives of hours to days in vivo , it has also been demonstrated that mature miRNA species from miR-17~92 do not respond consistently to miR-17~92 depletion (41–43) and that the secondary structure of the miR-17~92 primary transcript affects miRNA processing (44). The lack of response to the miR-92a inhibitor in mouse cells derived from murine KRASmt and KRASmt/p53null lung tumors suggests that the interaction between the miR-92a inhibitor and the miR-17~92 primary transcript may differ between the two organisms.…”

Section: Discussionmentioning

confidence: 99%

Genetic Mutation of p53 and Suppression of the miR-17∼92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling

Borkowski

Zhao

et al. 2015

Cancer Research

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Lung cancer is the leading cause of cancer-related fatalities. Recent success developing genotypically-targeted therapies, with potency only in well-defined subpopulations of tumors, suggests a path to improving patient survival. We utilized a library of oligonucleotide inhibitors to microRNAs, a class of post-transcriptional gene regulators, to identify novel synthetic lethal interactions between miRNA inhibition and molecular mechanisms in NSCLC. Two inhibitors, those for miR-92a and miR-1226*, produced a toxicity distribution across a panel of 27 cell lines that correlated with loss of p53 protein expression. Notably, depletion of p53 was sufficient to confer sensitivity to otherwise resistant telomerase-immortalized bronchial epithelial cells. We found that both miR inhibitors cause sequence-specific down-regulation of the miR-17~92 polycistron, and this down-regulation was toxic only in the context of p53 loss. Mechanistic studies indicated the selective toxicity of miR-17~92 polycistron inactivation was the consequence of derepression of vitamin D signaling via suppression of CYP24A1; a rate limiting enzyme in the 1α,25-dihydroxyvitamin D3 metabolic pathway. Of note, high CYP24A1 expression significantly correlated with poor patient outcome in multiple lung cancer cohorts. Our results indicate that the screening approach utilized in this study can identify clinically relevant synthetic lethal interactions, and that vitamin D receptor agonists may show enhanced efficacy in p53-negative lung cancer patients.

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Section: Discussionmentioning

confidence: 99%

Genetic Mutation of p53 and Suppression of the miR-17∼92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling

Borkowski

Zhao

et al. 2015

Cancer Research

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“…E-Cad/ Lgr6 + single-cell injection in the kidney capsule produce differentiated bronchioalveolar tissue, while retaining self-renewal. 60 These cells may potentially act as endogenous lung stem cells. However, the use of both cells for lung recellularization has not been reported yet.…”

Section: Oeztuerk-winder and Colleagues Identified E-cad/lgr6mentioning

confidence: 99%

Future prospects for tissue engineered lung transplantation

et al. 2014

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“…Shortly after description of c-kit+ human lung stem cells, the existence of another population of putative stem cells was reported[14]. These cells were characterized as positive for E-Cadherin and leucine-rich repeat-containing G-protein-coupled receptor 6 (E-Cad/Lgr6 + ) while being a sub-population of ITGA6 + cells.…”

Section: Lung Resident Stem/progenitor Cellsmentioning

confidence: 99%

Stem/progenitor cells and obstructive sleep apnea syndrome - new insights for clinical applications

Micheu

Rosca

Deleanu

2016

WJSC

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Obstructive sleep apnea syndrome (OSAS) is a widespread disorder, characterized by recurrent upper airway obstruction during sleep, mostly as a result of complete or partial pharyngeal obstruction. Due to the occurrence of frequent and regular hypoxic events, patients with OSAS are at increased risk of cardiovascular disease, stroke, metabolic disorders, occupational errors, motor vehicle accidents and even death. Thus, OSAS has severe consequences and represents a significant economic burden. However, some of the consequences, as well as their costs can be reduced with appropriate detection and treatment. In this context, the recent advances that were made in stem cell biology knowledge and stem cell - based technologies hold a great promise for various medical conditions, including respiratory diseases. However, the investigation of the role of stem cells in OSAS is still recent and rather limited, requiring further studies, both in animal models and humans. The goal of this review is to summarize the current state of knowledge regarding both lung resident as well as circulating stem/progenitor cells and discuss existing controversies in the field in order to identify future research directions for clinical applications in OSAS. Also, the paper highlights the requisite for inter-institutional, multi-disciplinary research collaborations in order to achieve breakthrough results in the field.

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Regulation of human lung alveolar multipotent cells by a novel p38α MAPK/miR-17-92 axis

Cited by 77 publications

References 43 publications

Genetic Mutation of p53 and Suppression of the miR-17∼92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling

Genetic Mutation of p53 and Suppression of the miR-17∼92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling

Future prospects for tissue engineered lung transplantation

Stem/progenitor cells and obstructive sleep apnea syndrome - new insights for clinical applications

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