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.
Oncotarget. 2017 Apr 25*** epublish ***
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, Daniela Marzioni
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy., Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy., Centre of Epidemiology, Biostatistics and Medical Information Technology, Università Politecnica delle Marche, Ancona, Italy., Unit of Cancer Pathology, CeSI-MeT, "G. d'Annunzio" University, Chieti, Italy., Department of Clinical Sciences, DISCO, Università Politecnica delle Marche, Ancona, Italy., Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, United Hospitals, Ancona, Italy.