High levels of hypusinated eIF5A in leiomyoma and leiomyosarcoma pathologies: a possible novel therapeutic target.

Autor: Greco S; Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy., Zannotti A; Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy; Department of Specialist and Odontostomatological Clinical Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy., Pellegrino P; Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy., Giantomassi F; Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60126 Ancona, Italy., Delli Carpini G; Department of Specialist and Odontostomatological Clinical Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy., D'Agostino M; Department of Life and Environmental Sciences, New York-Marche Structural Biology Center (NY, MaSBIC), Università Politecnica delle Marche, 60131 Ancona, Italy., Goteri G; Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60126 Ancona, Italy., Ciavattini A; Department of Specialist and Odontostomatological Clinical Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy., Donati C; Department of Experimental and Clinical Biomedical Sciences 'M. Serio', Università di Firenze, 50134 Firenze, Italy., Bernacchioni C; Department of Experimental and Clinical Biomedical Sciences 'M. Serio', Università di Firenze, 50134 Firenze, Italy., Petraglia F; Department of Experimental and Clinical Biomedical Sciences 'M. Serio', Università di Firenze, 50134 Firenze, Italy., La Teana A; Department of Life and Environmental Sciences, New York-Marche Structural Biology Center (NY, MaSBIC), Università Politecnica delle Marche, 60131 Ancona, Italy., Ciarmela P; Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy. Electronic address: p.ciarmela@univpm.it.
Jazyk: angličtina
Zdroj: Reproductive biomedicine online [Reprod Biomed Online] 2023 Jul; Vol. 47 (1), pp. 15-25. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1016/j.rbmo.2023.03.017
Abstrakt: Research Question: Is the hypusinated form of the eukaryotic translation initiation factor 5A (EIF5A) present in human myometrium, leiomyoma and leiomyosarcoma, and does it regulate cell proliferation and fibrosis?
Design: The hypusination status of eIF5A in myometrial and leiomyoma patient-matched tissues was evaluated by immunohistochemistry and Western blotting as well as in leiomyosarcoma tissues by immunohistochemistry. Myometrial, leiomyoma and leiomyosarcoma cell lines were treated with N1-guanyl-1,7-diaminoheptane (GC-7), responsible for the inhibition of the first step of eIF5A hypunization, and the proliferation rate was determined by MTT assay; fibronectin expression was analysed by Western blotting. Finally, expression of fibronectin in leiomyosarcoma tissues was detected by immunohistochemistry.
Results: The hypusinated form of eIF5A was present in all tissues examined, with an increasing trend of hypusinated eIF5A levels from normal myometrium to neoplastic benign leiomyoma up to neoplastic malignant leiomyosarcoma. The higher levels in leiomyoma compared with myometrium were confirmed by Western blotting (P = 0.0046). The inhibition of eIF5A hypusination, with GC-7 treatment at 100 nM, reduced the cell proliferation in myometrium (P = 0.0429), leiomyoma (P = 0.0030) and leiomyosarcoma (P = 0.0044) cell lines and reduced the expression of fibronectin in leiomyoma (P = 0.0077) and leiomyosarcoma (P = 0.0280) cells. The immunohistochemical staining of leiomyosarcoma tissue revealed that fibronectin was highly expressed in the malignant aggressive (central) part of the leiomyosarcoma lesion, where hypusinated eIF5A was also highly represented.
Conclusions: These data support the hypothesis that eIF5A may be involved in the pathogenesis of myometrial benign and malignant pathologies.
(Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: