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Open AccessArticle

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

1
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
2
Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
3
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy
4
General and Oncologic Surgery, Department of Surgery, G.B. Morgagni L.Pierantoni General Hospital, AUSL Romagna, 47121 Forlì, Italy
5
Department of Pathology, AUSL Romagna, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
6
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4452; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184452
Received: 26 August 2019 / Revised: 3 September 2019 / Accepted: 5 September 2019 / Published: 10 September 2019
(This article belongs to the Special Issue Activations of Cadherin Signaling in 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 (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. View Full-Text
Keywords: E-cadherin; CDH1; intestinal-type gastric cancer; microRNAs E-cadherin; CDH1; intestinal-type gastric cancer; microRNAs
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MDPI and ACS Style

Rossi, T.; Tedaldi, G.; Petracci, E.; Abou Khouzam, R.; Ranzani, G.N.; Morgagni, P.; Saragoni, L.; Monti, M.; Calistri, D.; Ulivi, P.; Molinari, C. E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer. Int. J. Mol. Sci. 2019, 20, 4452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184452

AMA Style

Rossi T, Tedaldi G, Petracci E, Abou Khouzam R, Ranzani GN, Morgagni P, Saragoni L, Monti M, Calistri D, Ulivi P, Molinari C. E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer. International Journal of Molecular Sciences. 2019; 20(18):4452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184452

Chicago/Turabian Style

Rossi, Tania; Tedaldi, Gianluca; Petracci, Elisabetta; Abou Khouzam, Raefa; Ranzani, Guglielmina N.; Morgagni, Paolo; Saragoni, Luca; Monti, Manlio; Calistri, Daniele; Ulivi, Paola; Molinari, Chiara. 2019. "E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer" Int. J. Mol. Sci. 20, no. 18: 4452. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184452

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