Association of H3K4me3 and CBX7 Levels to the Down-Regulation of <i>GKN</i>1 Gene Expression in Gastric Cancer Cells

• 作者: Antonella Federico Chiara Stella Di Stadio Emilia Rippa Filomena Altieri Giuseppina Miselli Maurizio Grillo Paolo Arcari
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: CBX7 Gastrokine 1 Gastric Cancer EPIGENETICS H3K4 Methylation
• 年，卷（期）: 2019,（5）
• 页码范围: 146-156
• 页数: 11页
• 分类号: R73

摘要

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.