Avellini Chiara, Licini Caterina, Lazzarini Raffaella, Gesuita Rosaria, Guerra Emanuela, Tossetta Giovanni, Castellucci Clara, Giannubilo Stefano Raffaele, Procopio Antonio, Alberti Saverio, Mazzucchelli Roberta, Olivieri Fabiola, Marzioni Daniela
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.
Oncotarget. 2017 Apr 25;8(35):58642-58653. doi: 10.18632/oncotarget.17407. eCollection 2017 Aug 29.
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 . 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. 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.
人滋养层细胞表面抗原2(Trop-2)是一种40 kDa的跨膜糖蛋白,最初被鉴定为人滋养层细胞的标志物。Trop-2通过激活多种细胞内信号通路来作用于细胞增殖、黏附和迁移。在几种类型的癌症中均已证实Trop-2表达升高,且与侵袭性和不良预后相关。由于尚无关于膀胱癌(BC)中Trop-2的相关数据,本研究的目的是确定其在正常个体和不同阶段BC患者组织标本中的水平。此外,根据最近的证据,Trop-2是miR-125b的靶标,因此还对组织标本中的miR-125b表达进行了评估。最后,评估了Trop-2/miR-125b轴对BC细胞增殖和迁移的影响。结果发现,Trop-2/miR-125b轴在正常尿路上皮、非侵袭性BC和侵袭性BC组织中的表达存在差异。BC组织中miR-125b的显著下调与Trop-2蛋白水平的显著升高相关,并与疾病严重程度相关。分析证实了miR-125b在下调Trop-2蛋白水平中的作用,并表明Trop-2/miR-125b轴影响膀胱组织中的细胞增殖。总之,我们的研究结果突出了Trop-2/miR-125b轴在BC进展中的作用,并提示Trop-2和miR-125b作为诊断/预后标志物候选物以及创新治疗方法的可药物靶向靶点。