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miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()

Gastroduodenal refluxate found in the upper aerodigestive tract is not clinically uncommon. We recently demonstrated the neoplastic potential of gastroduodenal fluids (GDF) on hypopharyngeal mucosa, via NF-κB, using in vitro and in vivo models. Here we will explore the in vivo effect of GDF on laryn...

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Detalles Bibliográficos
Autores principales: Sasaki, Clarence T., Vageli, Dimitra P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909705/
https://www.ncbi.nlm.nih.gov/pubmed/27292022
http://dx.doi.org/10.1016/j.neo.2016.04.007
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author Sasaki, Clarence T.
Vageli, Dimitra P.
author_facet Sasaki, Clarence T.
Vageli, Dimitra P.
author_sort Sasaki, Clarence T.
collection PubMed
description Gastroduodenal refluxate found in the upper aerodigestive tract is not clinically uncommon. We recently demonstrated the neoplastic potential of gastroduodenal fluids (GDF) on hypopharyngeal mucosa, via NF-κB, using in vitro and in vivo models. Here we will explore the in vivo effect of GDF on laryngeal mucosa (LM) to induce early preneoplastic lesions related to NF-κB activation, along with deregulation of specific microRNA (miRNA) markers previously linked to laryngeal cancer. We used histological, immunohistochemical, automated quantitative analysis and quantitative polymerase chain reaction to examine LM from 35 C57Bl/6J mice previously treated with topical GDF against corresponding controls (4 experimental and 3 control groups; 5 mice/group). Our analysis showed that GDF produced early preneoplastic lesions in treated LM related to NF-κB activation. LM treated by acid and bile combination demonstrated significantly higher expression of the analyzed cell proliferation markers (Ki67, CK14, ∆Np63), oncogenic p-STAT3, and changes of cell adhesion molecules (E-cadherin, ϐ-catenin) versus untreated LM or LM exposed to acid alone (P < .0005). Furthermore, acidic bile but not neutral bile appeared to accelerate the expression of “oncomirs” miR-21, miR-155, and miR-192 (acidic bile versus neutral bile, P < .0001), while reducing tumor suppressor miR-375 (acidic bile versus neutral bile, P = .0137), previously linked to NF-κB and laryngeal cancer. Finally, acidic bile induced reduction of miR-34a, miR-375, and miR-451a, exhibiting an inverse correlation with NF-κB activation. SIGNIFICANCE: Bile in combination with acid has a selective tumorigenic effect on LM, inducing deregulation of “oncomirs” and tumor suppressor miRNAs, produced by NF-κB activation with molecular and early histopathological alterations linked to neoplastic transformation. Systematic acid suppression may in part convey a protective role.
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spelling pubmed-49097052016-06-22 miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo() Sasaki, Clarence T. Vageli, Dimitra P. Neoplasia Original article Gastroduodenal refluxate found in the upper aerodigestive tract is not clinically uncommon. We recently demonstrated the neoplastic potential of gastroduodenal fluids (GDF) on hypopharyngeal mucosa, via NF-κB, using in vitro and in vivo models. Here we will explore the in vivo effect of GDF on laryngeal mucosa (LM) to induce early preneoplastic lesions related to NF-κB activation, along with deregulation of specific microRNA (miRNA) markers previously linked to laryngeal cancer. We used histological, immunohistochemical, automated quantitative analysis and quantitative polymerase chain reaction to examine LM from 35 C57Bl/6J mice previously treated with topical GDF against corresponding controls (4 experimental and 3 control groups; 5 mice/group). Our analysis showed that GDF produced early preneoplastic lesions in treated LM related to NF-κB activation. LM treated by acid and bile combination demonstrated significantly higher expression of the analyzed cell proliferation markers (Ki67, CK14, ∆Np63), oncogenic p-STAT3, and changes of cell adhesion molecules (E-cadherin, ϐ-catenin) versus untreated LM or LM exposed to acid alone (P < .0005). Furthermore, acidic bile but not neutral bile appeared to accelerate the expression of “oncomirs” miR-21, miR-155, and miR-192 (acidic bile versus neutral bile, P < .0001), while reducing tumor suppressor miR-375 (acidic bile versus neutral bile, P = .0137), previously linked to NF-κB and laryngeal cancer. Finally, acidic bile induced reduction of miR-34a, miR-375, and miR-451a, exhibiting an inverse correlation with NF-κB activation. SIGNIFICANCE: Bile in combination with acid has a selective tumorigenic effect on LM, inducing deregulation of “oncomirs” and tumor suppressor miRNAs, produced by NF-κB activation with molecular and early histopathological alterations linked to neoplastic transformation. Systematic acid suppression may in part convey a protective role. Neoplasia Press 2016-05-25 /pmc/articles/PMC4909705/ /pubmed/27292022 http://dx.doi.org/10.1016/j.neo.2016.04.007 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Sasaki, Clarence T.
Vageli, Dimitra P.
miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title_full miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title_fullStr miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title_full_unstemmed miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title_short miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo()
title_sort mir-21, mir-155, mir-192, and mir-375 deregulations related to nf-kappab activation in gastroduodenal fluid–induced early preneoplastic lesions of laryngeal mucosa in vivo()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909705/
https://www.ncbi.nlm.nih.gov/pubmed/27292022
http://dx.doi.org/10.1016/j.neo.2016.04.007
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