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

// Kwang-Soo Lee 1,2,* , Jong-Lyul Park 3,4,* , Kwanbok Lee 1 , Lauren E. Richardson 1,5 , Betty H. Johnson 1 , Hyun-Sung Lee 6 , Ju-Seog Lee 6 , Sang-Bae Kim 6 , Oh-Hyung Kwon 3 , Kyu Sang Song 7 , Yong Sung Kim 3,4 , Hassan Ashktorab 8 , Duane T. Smoot 8 , Sung Ho Jeon 2 , Seon-Young Kim 3,4 and Yong Sun Lee 1 1. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX77555-1072, USA 2. Department of Life Science and Center for Aging and Health Care, Hallym University, Chuncheon 200-702, Korea 3. Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea 4. Department of Functional Genomics, University of Science and Technology, Daejeon, 305-806, Korea 5. Lamar University, Beaumont, TX77710, USA 6. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 7. Department of Pathology, College of Medicine, Chungnam National University, Daejeon, 301-747, Korea 8. Departments of Medicine, Howard University, Washington, D. C., 20060 USA * co-first authors Correspondence: Yong Sun Lee, email: // Seon-Young Kim, email: // Sung Ho Jeon, email: // Keywords : nc886, gastric cancer, CpG DNA methylation, cell proliferation, tumor suppressor Received : May 26, 2014 Accepted : May 30, 2014 Published : May 31, 2014 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.