Cargando…

E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer

CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miR...

Descripción completa

Detalles Bibliográficos
Autores principales: Rossi, Tania, Tedaldi, Gianluca, Petracci, Elisabetta, Abou Khouzam, Raefa, Ranzani, Guglielmina Nadia, Morgagni, Paolo, Saragoni, Luca, Monti, Manlio, Calistri, Daniele, Ulivi, Paola, Molinari, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769612/
https://www.ncbi.nlm.nih.gov/pubmed/31509966
http://dx.doi.org/10.3390/ijms20184452
_version_ 1783455278258192384
author Rossi, Tania
Tedaldi, Gianluca
Petracci, Elisabetta
Abou Khouzam, Raefa
Ranzani, Guglielmina Nadia
Morgagni, Paolo
Saragoni, Luca
Monti, Manlio
Calistri, Daniele
Ulivi, Paola
Molinari, Chiara
author_facet Rossi, Tania
Tedaldi, Gianluca
Petracci, Elisabetta
Abou Khouzam, Raefa
Ranzani, Guglielmina Nadia
Morgagni, Paolo
Saragoni, Luca
Monti, Manlio
Calistri, Daniele
Ulivi, Paola
Molinari, Chiara
author_sort Rossi, Tania
collection PubMed
description CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miRs) are involved in its transcriptional control. We evaluated CDH1 expression by quantitative real-time PCR (RT-qPCR) in 33 IGC patients and found a significant downregulation in tumor tissues compared to normal counterparts (p-value = 0.025). Moreover, 14 miRs, predicted to be involved in CDH1 regulation in both a direct and indirect manner, were selected and analyzed by RT-qPCR in an independent case series of 17 IGCs and matched normal tissues. miR-101, miR-26b, and miR-200c emerged as significantly downregulated and were confirmed in the case series of 33 patients (p-value < 0.001). Finally, we evaluated EZH2 expression, a target of both miR-101 and miR-26b, which showed significant upregulation in IGCs (p-value = 0.005). A significant inverse correlation was observed between EZH2 overexpression and CDH1, miR-101, and miR-26b levels (p-value < 0.001). Our results reinforce the link between CDH1 and IGC, highlighting the role of miRs in its transcriptional control and improving our understanding of GC subtypes and biomarkers.
format Online
Article
Text
id pubmed-6769612
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-67696122019-10-30 E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer Rossi, Tania Tedaldi, Gianluca Petracci, Elisabetta Abou Khouzam, Raefa Ranzani, Guglielmina Nadia Morgagni, Paolo Saragoni, Luca Monti, Manlio Calistri, Daniele Ulivi, Paola Molinari, Chiara Int J Mol Sci Article CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miRs) are involved in its transcriptional control. We evaluated CDH1 expression by quantitative real-time PCR (RT-qPCR) in 33 IGC patients and found a significant downregulation in tumor tissues compared to normal counterparts (p-value = 0.025). Moreover, 14 miRs, predicted to be involved in CDH1 regulation in both a direct and indirect manner, were selected and analyzed by RT-qPCR in an independent case series of 17 IGCs and matched normal tissues. miR-101, miR-26b, and miR-200c emerged as significantly downregulated and were confirmed in the case series of 33 patients (p-value < 0.001). Finally, we evaluated EZH2 expression, a target of both miR-101 and miR-26b, which showed significant upregulation in IGCs (p-value = 0.005). A significant inverse correlation was observed between EZH2 overexpression and CDH1, miR-101, and miR-26b levels (p-value < 0.001). Our results reinforce the link between CDH1 and IGC, highlighting the role of miRs in its transcriptional control and improving our understanding of GC subtypes and biomarkers. MDPI 2019-09-10 /pmc/articles/PMC6769612/ /pubmed/31509966 http://dx.doi.org/10.3390/ijms20184452 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rossi, Tania
Tedaldi, Gianluca
Petracci, Elisabetta
Abou Khouzam, Raefa
Ranzani, Guglielmina Nadia
Morgagni, Paolo
Saragoni, Luca
Monti, Manlio
Calistri, Daniele
Ulivi, Paola
Molinari, Chiara
E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title_full E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title_fullStr E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title_full_unstemmed E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title_short E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer
title_sort e-cadherin downregulation and micrornas in sporadic intestinal-type gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769612/
https://www.ncbi.nlm.nih.gov/pubmed/31509966
http://dx.doi.org/10.3390/ijms20184452
work_keys_str_mv AT rossitania ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT tedaldigianluca ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT petraccielisabetta ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT aboukhouzamraefa ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT ranzaniguglielminanadia ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT morgagnipaolo ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT saragoniluca ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT montimanlio ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT calistridaniele ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT ulivipaola ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer
AT molinarichiara ecadherindownregulationandmicrornasinsporadicintestinaltypegastriccancer