nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer

Kwang Soo Lee, Jong Lyul Park, Kwanbok Lee, Lauren E. Richardson, Betty H. Johnson, Hyun Sung Lee, Ju Seog Lee, Sang Bae Kim, Oh Hyung Kwon, Kyu Sang Song, Yong Sung Kim, Hassan Ashktorab, Duane T. Smoot, Sung Ho Jeon, Seon Young Kim, Yong Sun Lee

Research output: Contribution to journalArticle

Abstract

nc886 is a 101 nucleotide long non-coding RNA that has been designated as a precursor microRNA or a vault RNA based upon it sequence. nc886 has also been suggested to be a tumor suppressor, mainly inferred by its expression pattern as well as its genomic location at human chromosome 5q31, a locus for a tumor suppressor gene(s). However, legitimate data based on nc886's correct identity for its functional cellular roles as a tumor suppressor have not been provided yet. Here we have investigated nc886 in gastric cancer where its expression is suppressed due to CpG DNA hypermethylation at its promoter region in a cohort of paired tumor/normal tissues from 88 gastric cancer patients. CpG hypermethylation of nc886 and thus its diminished expression is significantly associated with poor survival in these cancer patients. nc886 inhibits cell proliferation when ectopically expressed in gastric cancer cells. nc886's tumor suppressive role is corroborated by the induction of well-known oncogenes such as FOS, NF-κB, and MYC upon its knockdown. All these activities of nc886 are undoubtedly independent of mature microRNA or vault RNA. Our data indicate that nc886 is a putative tumor suppressor and could potentially be used as a diagnostic marker in gastric cancer.

Original languageEnglish (US)
Pages (from-to)3944-3955
Number of pages12
JournalOncotarget
Volume5
Issue number11
DOIs
StatePublished - 2014

Keywords

  • Cell proliferation
  • CpG DNA methylation
  • Gastric cancer
  • Tumor suppressor
  • nc886

ASJC Scopus subject areas

  • Oncology

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    Lee, K. S., Park, J. L., Lee, K., Richardson, L. E., Johnson, B. H., Lee, H. S., Lee, J. S., Kim, S. B., Kwon, O. H., Song, K. S., Kim, Y. S., Ashktorab, H., Smoot, D. T., Jeon, S. H., Kim, S. Y., & Lee, Y. S. (2014). nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. Oncotarget, 5(11), 3944-3955. https://doi.org/10.18632/oncotarget.2047