TITLE:
Association of H3K4me3 and CBX7 Levels to the Down-Regulation of GKN1 Gene Expression in Gastric Cancer Cells
AUTHORS:
Chiara Stella Di Stadio, Filomena Altieri, Antonella Federico, Giuseppina Miselli, Maurizio Grillo, Emilia Rippa, Paolo Arcari
KEYWORDS:
CBX7, Gastrokine 1, Gastric Cancer, Epigenetics, H3K4 Methylation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.7 No.5,
May
21,
2019
ABSTRACT: Gastrokine
1 (GKN1) is a highly secreted gastric
mucosal protein in normal individuals but strongly down-regulated or totally
absent in gastric cancer subjects. An epigenetic mechanism might be responsible
for GKN1 gene silencing probably
through the activity of a transcription factor in association with the enzymes SUV39H1 and HDACs on the GKN1 promoter. In fact, compared to non-tumor tissues, a high increase of H3K9me3
level was observed in the corresponding tumor ones. Because H3K4me3 seems to be
a possible epigenetic mark for active euchromatin, we try to verify the H3K4me3
level on the GKN1 promoter in gastric cancer tumor specimens. In
addition, we also attempt to highlight if CBX7 could be the possible regulatory
transcription factor correlated to GKN1 gene promoter. Therefore, we
evaluated if the CBX7 expression levels could be associated with GKN1
down-regulation in gastric cancer. To this purpose, 2 pairs of non-tumor and
tumor surgical specimens from patients with gastric cancer were analyzed for
H3K4me3 by chromatin immunoprecipitation (ChiP) assays, and 9 pairs were
instead analyzed by Western blotting for GKN1, and CBX7 expression levels,
respectively. The results suggested that the observed increase of H3K4me3 in
tumor samples was not in agreement with its proposed function whereas the
expression of CBX7 was not associated with the down-regulation of GKN1. In
particular, the expression levels of CBX7 in tumor samples might suggest a
survival role in gastric cancer.