E-cadherin downregulation and microRNAs in sporadic intestinal-type gastric cancer

Tania Rossi, Gianluca Tedaldi, Elisabetta Petracci, Raefa Abou Khouzam, Guglielmina Nadia Ranzani, Paolo Morgagni, Luca Saragoni, Manlio Monti, Daniele Calistri, Paola Ulivi, Chiara Molinari

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number4452
JournalInternational Journal of Molecular Sciences
Volume20
Issue number18
DOIs
Publication statusPublished - Sep 2 2019

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Keywords

  • CDH1
  • E-cadherin
  • Intestinal-type gastric cancer
  • microRNAs

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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