title: Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis.
abstract: nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppressor in esophageal squamous cell carcinoma (ESCC). In 84 paired specimens from ESCC patients, nc886 expression is significantly lower in tumors than their normal adjacent tissues. More importantly, decreased expression of nc886 is significantly associated with shorter recurrence-free survival of the patients. Suppression of nc886 is mediated by CpG hypermethylation of its promoter, as evidenced by its significant negative correlation to nc886 expression in ESCC tumors and by induced expression of nc886 upon demethylation of its promoter. Knockdown of nc886 and consequent PKR activation induce FOS and MYC oncogenes as well as some inflammatory genes including oncogenic NF-κB. When ectopically expressed, nc886 inhibits proliferation of ESCC cells, further demonstrating that nc886 could be a tumor suppressor. All these findings implicate nc886 as a novel, putative tumor suppressor that is epigenetically silenced and regulates the expression of oncogenes in ESCC.
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, 410-769, Korea.
authors.forename: Hyun-Sung
authors.initials: HS
authors.lastname: Lee
authors.forename: Kwanbok
authors.initials: K
authors.lastname: Lee
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Jang
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Park
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Betty H
authors.initials: BH
authors.lastname: Johnson
authors.forename: Jae Iii
authors.initials: JI
authors.lastname: Zo
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX77555-1072, USA.
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009857:Oncogenes; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D022661:RNA, Untranslated