NDRG2, suppressed expression associates with poor prognosis in pancreatic cancer, is hypermethylated in the second promoter in human gastrointestinal cancers

Akihiro Yamamura, Koh Miura, Hideaki Karasawa, Fuyuhiko Motoi, Yasuhiko Mizuguchi, Yuriko Saiki, Shinichi Fukushige, Makoto Sunamura, Chikashi Shibata, Michiaki Unno, Akira Horii

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Although N-myc downstream regulated gene 2 (NDRG2) is frequently downregulated in various cancers and is considered to be a candidate tumor suppressor gene, molecular mechanisms of the expressional suppression that lead to cancers are largely unknown. Recent studies indicated that epigenetic suppression of NDRG2 involved carcinogenesis and progression in several tumor types, and we demonstrated positive association with NDRG2 suppression and poor prognosis in pancreatic cancer. In this study, we analyzed mRNA and protein expressions of NDRG2 in 26 cancer cell lines (20 colorectal and 6 gastric cancers) and found that many cell lines showed variously reduced NDRG2 expressions. Furthermore, NDRG2 expressions were significantly reduced in primary resected cancer tissues compared to corresponding normal tissues immunohistochemically (19 of 20 colorectal and 14 of 17 gastric cancers). Treatment with 5-Aza-2′ deoxycytidine predominantly upregulated NDRG2 expressions in NDRG2 low-expressing cell lines. Bisulfite sequencing analyses and methylation specific PCR revealed that methylation status at one of the two promoters (around exon 2) correlated well with the suppressed expression, and this is the major promoter in colorectal and gastric cancer cell lines. Our present results suggest that hypermethylation in promoter around exon 2 is functioning as essential factors of NDRG2 silencing in gastrointestinal cancers.

Original languageEnglish
Pages (from-to)138-143
Number of pages6
JournalBiochemical and biophysical research communications
Volume484
Issue number1
DOIs
Publication statusPublished - 2017 Feb 26

Keywords

  • Gastrointestinal cancers
  • Hypermethylation
  • NDRG2
  • Type II transcript

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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