Slight increase in ROS levels increases global DNA methylation and changes the methylation status of genes related to WNT and Shh pathways in cancer stem cells of human pancreatic adenocarcinoma


Sancar S., Erçin M., Oktayoğlu S., Özden S., Bolkent H. S., Bolkent Ş.

5th International Eurasian Conference on Biological and Chemical Sciences (EurasianBioChem 2022), Ankara, Türkiye, 23 - 25 Kasım 2022, ss.1730, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1730
  • İstanbul Üniversitesi Adresli: Evet

Özet

During carcinogenesis, epigenetic alterations contribute to malignant properties that leads to inappropriate silencing or

activation of cancer-associated genes. There are limited number of studies investigating the relationship of a slight

increase in the level of ROS production in cancer stem cells with the regulation of DNA methylation. We aimed to

investigate whether a slight increase in ROS levels changes methylation status at CpG sites in the promoters of more than

200 genes related to stemness, metabolism, signaling pathways, epithelial-mesenchymal transition, drug transporters,

antioxidant enzymes, and glycosyltransferases. PANC-1 cells were treated with 0.1 mM H2O2 for 24h and cancer stem

cells were sorted by their ALDEFLOUR positivity. After DNA isolation, methylated DNA was immunoprecipitated and

labeled. Methylated promoters were detected by microarray and analyzed bioinformatically. Besides any changes in

global DNA methylation were also researched following H2O2 treatment. The promoters of genes related to Wnt and

Sonic hedgehog (Shh) pathways were differently methylated in cancer stem cells exposed to 0.1 mM H2O2. The levels of

5-mC increased in the experimental group compared to the control. These results suggest that slight increase in ROS level

may lead to epigenetic changes via DNA methylation in pancreatic cancer stem cells and effect the properties of stemness.

Keywords: Cancer stem cell, reactive oxygen species, stemness, MeDIP array, global DNA methylation.