Abstract 529: nc886, a noncoding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer

Abstract

Abstract nc886, a novel type of non-coding RNA, was initially identified as a microRNA precursor or a vault RNA, but it has been shown to be distinct from them and rather to be a cellular RNA ligand and inhibitor of PKR (Protein Kinase RNA-activated). PKR's roles in viral infection, cellular stresses, and cancer are well documented. 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). 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 and a battery of gastric cell lines. 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 nc886 knockdown. All these activities of nc886 are undoubtedly independent of mature microRNA or vault RNA, but presumably through PKR that is typically activated by viral infection and cellular stresses upon which those oncogenes are known to be induced. Our data indicate that nc886 is a tumor suppressor and could potentially be used as a diagnostic marker and a therapeutic agent in gastric cancer. Citation Format: Jong-Lyul Park, Yong Sung Kim, Seon-Young Kim, Kwang Soo Lee, Sung Ho Jeon, Kwanbok Lee, Yong Sun Lee. nc886, a noncoding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 529. doi:10.1158/1538-7445.AM2014-529