Oncotarget

Research Papers:

The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer

Chiara Avellini, Caterina Licini, Raffaella Lazzarini, Rosaria Gesuita, Emanuela Guerra, Giovanni Tossetta, Clara Castellucci, Stefano Raffaele Giannubilo, Antonio Procopio, Saverio Alberti, Roberta Mazzucchelli, Fabiola Olivieri and Daniela Marzioni _

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Oncotarget. 2017; 8:58642-58653. https://doi.org/10.18632/oncotarget.17407

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Abstract

Chiara Avellini1,*, Caterina Licini1,*, Raffaella Lazzarini2, Rosaria Gesuita3, Emanuela Guerra4,5, Giovanni Tossetta1, Clara Castellucci2, Stefano Raffaele Giannubilo6, Antonio Procopio2,7, Saverio Alberti4,5, Roberta Mazzucchelli8, Fabiola Olivieri2,7,* and Daniela Marzioni1,*

1Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy

2Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy

3Centre of Epidemiology, Biostatistics and Medical Information Technology, Università Politecnica delle Marche, Ancona, Italy

4Unit of Cancer Pathology, CeSI-MeT, “G. d'Annunzio” University, Chieti, Italy

5ONCOXX Biotech SRL, Chieti, Italy

6Department of Clinical Sciences, DISCO, Università Politecnica delle Marche, Ancona, Italy

7Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy

8Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, United Hospitals, Ancona, Italy

*These authors have contributed equally to this work

Correspondence to:

Daniela Marzioni, email: d.marzioni@univpm.it

Keywords: bladder cancer, Trop-2, miR-125b, miRNA, immunohistochemistry

Received: January 27, 2017     Accepted: March 30, 2017     Published: April 25, 2017

ABSTRACT

Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages. Moreover, since according to recent evidence Trop-2 is a miR-125b target, miR-125b expression was also assessed in tissue specimens. Finally, the effect of the Trop-2/miR-125b axis on the proliferation and migration of BC cells was evaluated in vitro.

The Trop-2/miR-125b axis was seen to be differentially expressed in normal urothelium, non-invasive BC and invasive BC tissue. Significant miR-125b down-regulation was associated with a significant increase in Trop-2 protein levels in BC tissue and correlated with disease severity. In vitro analysis confirmed the role of miR-125b in down-modulation of Trop-2 protein levels and showed that Trop-2/miR-125b axis affects cellular proliferation in bladder tissue.

In conclusion, our findings highlight a role for the Trop-2/miR-125b axis in BC progression and suggest Trop-2 and miR-125b as diagnostic/prognostic marker candidates as well as druggable targets for innovative therapeutic approaches.


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