Embryonic microenvironment suppresses YY1 and YY1-related genes in prostate cancer stem cells.

Autor: Taskiran A; Ege University Faculty of Medicine Department of Histology and Embryology, İzmir 35100, Turkey., Oktem G; Ege University Faculty of Medicine Department of Histology and Embryology, İzmir 35100, Turkey; Ege University Institute of Health Sciences Department of Stem Cell, İzmir 35100, Turkey., Demir A; Ege University Faculty of Medicine Department of Histology and Embryology, İzmir 35100, Turkey., Oltulu F; Ege University Faculty of Medicine Department of Histology and Embryology, İzmir 35100, Turkey., Ozcinar E; İzmir Tinaztepe University Department of Histology and Embryology, İzmir 35400, Turkey., Duzagac F; University of Texas MD Anderson Cancer Center, Department of Clinical Cancer Prevention, Texas, Houston, TX 77030, USA., Guven U; Università degli Studi di Milano Department of Biosciences, Milan 20122, Italy., Karakoc E; Wellcome Sanger Institute Translational Cancer Genomics, Hinxton, Cambridge CB10 1SA, UK., Cakir A; Istanbul Medipol University Faculty of Medicine Department of Pathology, İstanbul 34810, Turkey., Ayla S; Istanbul Medeniyet University Faculty of Medicine Department of Histology and Embryology, İstanbul 34700, Turkey., Guven S; Necmettin Erbakan University Meram Medical Faculty Department of Urology, Konya 42090, Turkey., Acikgoz E; Van Yuzuncu Yil University, Faculty of Medicine, Department of Histology and Embryology, Van 65090, Turkey. Electronic address: edaacikgoz@yyu.edu.tr.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2024 Aug; Vol. 260, pp. 155467. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1016/j.prp.2024.155467
Abstrakt: Yin yang 1 (YY1), a transcription factor, plays crucial roles in cell fate specification, differentiation, and pluripotency during embryonic development. It is also involved in tumorigenesis, drug resistance, metastasis, and relapse caused by cancer stem cells (CSCs), particularly in prostate cancer (PCa). Targeting YY1 could potentially eliminate prostate CSCs (PCSCs) and provide novel therapeutic approaches. PCa tissues often exhibit elevated YY1 expression levels, especially in high-grade cases. Notably, high-grade PCa tissues from 58 PCa patients and CD133 high /CD44 high PCSCs isolated from DU145 PCa cell line by FACS both showed significantly increased YY1 expression as observed through immunofluorescence staining, respectively. To investigate the embryonic microenvironment impact on YY1 expression in CSC populations, firstly PCSCs were microinjected into the inner cell mass of blastocysts and then PCSCs were co-cultured with blastocysts. Next Generation Sequencing was used to analyze alterations in YY1 and related gene expressions. Interestingly, exposure to the embryonic microenvironment significantly reduced the expressions of YY1, YY2, and other relevant genes in PCSCs. These findings emphasize the tumor-suppressing effects of the embryonic environment by downregulating YY1 and YY1-related genes in PCSCs, thus providing promising strategies for PCa therapy. Through elucidating the mechanisms involved in embryonic reprogramming and its effects on YY1 expression, this research offers opportunities for further investigation into focused therapies directed against PCSCs, therefore enhancing the outcomes of PCa therapy. As a result, PCa tumors may benefit from YY1 and associated genes as a novel therapeutic target.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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