CTNNAL1 inhibits ozone‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Tan, Meiling; Liu, Caixia; Huang, Wenjie; Deng, Linhong; Qin, Xiaoqun; Xiang, Yang

doi:10.1113/ep086839

Cited by 14 publications

(14 citation statements)

References 39 publications

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“…We assayed wound healing after mechanical injury 28 to investigate repair activities in 16HBE14o- cells to investigate the influence of increased [Cl - ] i on airway wound repair. [Cl - ] i was clamped at the concentrations of 25 (resting [Cl - ] i ), 50, 70, and 100 mM.…”

Section: Resultsmentioning

confidence: 99%

Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

et al. 2020

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In the airway, Cl - is the most abundant anion and is critically involved in transepithelial transport. The correlation of the abnormal expression and activation of chloride channels (CLCs), such as cystic fibrosis transmembrane conductance regulators (CFTRs), anoctamin-1, and CLC-2, with cell migration capability suggests a relationship between defective Cl - transport and epithelial wound repair. However, whether a correlation exists between intracellular Cl - and airway wound repair capability has not been explored thus far, and the underlying mechanisms involved in this relationship are not fully defined. Methods: In this work, the alteration of intracellular chloride concentration ([Cl - ] i ) was measured by using a chloride-sensitive fluorescent probe (N-[ethoxycarbonylmethyl]-6-methoxyquinolium bromide). Results: We found that clamping with high [Cl - ] i and 1 h of treatment with the CLC inhibitor CFTR blocker CFTR inh -172 and chloride intracellular channel inhibitor IAA94 increased intracellular Cl - concentration ([Cl - ] i ) in airway epithelial cells. This effect improved epithelial cell migration. In addition, increased [Cl - ] i in cells promoted F-actin reorganization, decreased cell stiffness, and improved RhoA activation and LIMK1/2 phosphorylation. Treatment with the ROCK inhibitor of Y-27632 and ROCK1 siRNA significantly attenuated the effects of increased [Cl - ] i on LIMK1/2 activation and cell migration. In addition, intracellular Ca 2+ concentration was unaffected by [Cl - ] i clamping buffers and CFTR inh -172 and IAA94. Conclusion: Taken together, these results suggested that Cl - accumulation in airway epithelial cells could activate the RhoA/ROCK/LIMK cascade to induce F-actin reorganization, down-regulate cell stiffness, and improve epithelial migration.

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Section: Resultsmentioning

confidence: 99%

Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

et al. 2020

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“…Keratin 13 (KRT13) is epigenetically suppressed during transforming growth factor-β 1-induced epithelial-mesenchymal transition [ 30 ]. The alpha-like 1 Catenin (CTNNAL1) (a cadherin-associated protein), an epithelial marker, are also under-expressed [ 31 ]. Myosin binding protein H (MYBPH) that inhibits cell motility and metastasis is also under-expressed, which is linked to the EMT phenotype [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

jouvence, a new human snoRNA involved in the control of cell proliferation

2020

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Background Small nucleolar RNAs (snoRNAs) are non-coding RNAs that are conserved from archaebacteria to mammals. They are associated in the nucleolus, with proteins to form small nucleolar ribonucleoprotein (snoRNPs). They modify ribosomal RNAs, for example, the H/ACA box that converts uridine to pseudouridine. In humans, various pathologies have been associated with snoRNAs, and several snoRNAs have been reported to participate in many cancer processes. Recently, a new H/ACA box snoRNA named jouvence has been identified in Drosophila and has been shown to be involved in lifespan determination in relation to gut homeostasis. Because snoRNAs are conserved through evolution, both structurally and functionally, a jouvence orthologue has been identified in humans. RT-PCR has revealed that jouvence is expressed, suggesting that it might be functional. These results suggest the hypothesis that jouvence may display similar functions, including increasing the healthy lifespan in humans. Results Here, we report the characterization of the human snoRNA jouvence, which has not yet been annotated in the genome. We show that its overexpression significantly stimulates cell proliferation, both in various stable cancerous cell lines as well as in primary cells. By contrast, its knockdown by siRNA leads to the opposite phenotype, a rapid decrease in cell proliferation. Transcriptomic analysis (RNA-Seq) revealed that the overexpression of jouvence leads to a dedifferentiation signature of the cells. Conversely, the knockdown of jouvence led to a striking decrease in the expression levels of genes involved in ribosome biogenesis and the spliceosome. Conclusion The overexpression of a single and short non-coding RNA of 159 nucleotides, the snoRNA-jouvence, seems to be sufficient to reorient cells toward stemness, while its depletion blocks cell proliferation. In this context, we speculate that the overexpression of jouvence, which appears to be a non-canonical H/ACA snoRNA, could represent a new tool to fight against the deleterious effects of aging, while inversely, its knockdown by siRNA could represent a new approach in cancer therapy.

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“…The Keratin 13 (KRT13) is epigenetically suppressed during Transforming Growth Factor-1-induced epithelial-mesenchymal transition [29]. The catenin (cadherin-associated protein), alpha-like 1 (CTNNAL1), an epithelial marker is also under-expressed [30]. The…”

Section: Hct116 Overexpressing H-jou Presents a Genomic Signature Of mentioning

confidence: 99%

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

El-Khoury

Bignon

Martin

2020

Preprint

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Small nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan.Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome.We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

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CTNNAL1 inhibits ozone‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Cited by 14 publications

References 39 publications

Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

jouvence, a new human snoRNA involved in the control of cell proliferation

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

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CTNNAL1 inhibits ozone‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Cited by 14 publications

References 39 publications

Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

jouvence, a new human snoRNA involved in the control of cell proliferation

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

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Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

Increased intracellular Cl^- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway