Current Issue

Volume 21, Number 2, Jul-Sep (Summer) 2019 , Serial Number: 82 Pages: 124-134

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


Fatemeh Shokraii, M.Sc, 1, 2, #, Maryam Moharrami, M.Sc, 3, #, Nasrin Motamed, Ph.D, 3, *, Maryam Shahhoseini, Ph.D, 4, Mehdi Totonchi, Ph.D, 4, Vahid Ezzatizadeh, Ph.D, 2, 5, Javad Firouzi, M.Sc., 2, Pardis Khosravani, M.Sc., 2, Marzieh Ebrahimi, Ph.D, 2, *,
Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
School of Biology, College of Science, University of Tehran, Tehran, Iran
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Medical Genetics, Royesh Medical Laboratory Centre, Tehran, Iran
*Corresponding Addresses: P.O.Box: 14155-6455 School of Biology College of Science University of Tehran Tehran Iran P.O.Box: 16635-148 Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Emails:motamed2@khayam.ut.ac.ir,mebrahimi@royaninstitute.org

The first two authors equally contributed to this work.

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+ CD49hi 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.