Histone Modification Marks Strongly Regulate CDH1 Promoter in Prostospheres as A Model of Prostate Cancer Stem Like Cells

Fatemeh Shokraii; Maryam Moharrami; Nasrin Motamed; Maryam Shahhoseini; Mehdi Totonchi; Vahid Ezzatizadeh; Javad Firouzi; Pardis Khosravani; Marzieh Ebrahimi

doi:10.22074/cellj.2019.5702

Histone Modification Marks Strongly Regulate CDH1 Promoter in Prostospheres as A Model of Prostate Cancer Stem Like Cells

Cell J. 2019 Jul;21(2):124-134. doi: 10.22074/cellj.2019.5702. Epub 2019 Feb 20.

Authors

Fatemeh Shokraii^#^{1

2}, Maryam Moharrami^#³, Nasrin Motamed⁴, Maryam Shahhoseini⁵, Mehdi Totonchi⁵, Vahid Ezzatizadeh^{2

6}, Javad Firouzi², Pardis Khosravani², Marzieh Ebrahimi⁷

Affiliations

¹ Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
² Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
³ School of Biology, College of Science, University of Tehran, Tehran, Iran.
⁴ School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic Adress:motamed2@khayam.ut.ac.ir.
⁵ Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
⁶ Department of Medical Genetics, Royesh Medical Laboratory Centre, Tehran, Iran.
⁷ Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic Address:mebrahimi@royaninstitute.org.

^# Contributed equally.

Abstract

Objective: Cadherin-1 (CDH1) plays an important role in the metastasis, while expression of this protein is under control of epigenetic changes on its gene promoter. Therefore we evaluated both DNA methylation (DNAmet) and histone modification marks of CDH1 in prostate cancer stem like cells (PCSLCs).

Materials and methods: In this experimental study, we isolated PCSLCs using cell surface marker and prostaspheroid formation, respectively. The cells isolated from both methods were characterized and then the levels of H3K4me2, H3K27me3, H3K9me2/3 and H3K9ac as well as DNAmet were assessed in CDH1 promoter of the isolated cells.

Results: The CD44⁺ CD49^hi cells were not validated as PCSLCs. However, prostaspheres overexpressed stemness related genes and had higher ability of invasion potential, associated with reduction in CDH1 expression. Epigenetic status analysis showed that CDH1 promoter was hypo-methylated. Histone modifications of H3K9ac and H3K4me3 were significantly reduced, in parallel with an increased level of H3K27me3.

Conclusion: Our results suggest that slight decrease of DNAmet of the CpG island in CDH1 promoter does not significantly contribute to the change of CDH1 expression. Therefore, histone modifications are responsible in repressing CDH1 in PCSLCs.

Keywords: CDH1; Cancer Stem Cells; Histone Modification; Methylation; Prostate Cancer.