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

Authors :
Tania Rossi
Gianluca Tedaldi
Elisabetta Petracci
Raefa Abou Khouzam
Guglielmina Nadia Ranzani
Paolo Morgagni
Luca Saragoni
Manlio Monti
Daniele Calistri
Paola Ulivi
Chiara Molinari
Source :
International Journal of Molecular Sciences, Vol 20, Iss 18, p 4452 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

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.

Details

Language :
English
ISSN :
14220067
Volume :
20
Issue :
18
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.648ba2c3a43144d8aff7bfb931410a58
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms20184452