title: Promoter hypermethylation-mediated downregulation of miR-770 and its host gene MEG3, a long non-coding RNA, in the development of gastric cardia adenocarcinoma.
abstract: Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes an lncRNA and is downregulated in an expanding list of cancer cell lines and primary human cancers. The miR-770 is transcribed from the intronic sequence of MEG3 and MEG3 may be the host gene for miR-770. However, the biological role of MEG3 and miR-770 in gastric cardia adenocarcinoma (GCA) development and prognosis is poorly defined. The present study was to investigate the function and methylation status of MEG3 in GCA, and further to detect the functional association of miR-770 and its host gene MEG3 in GCA carcinogenesis and prognosis. MEG3 and miR-770 was significantly downregulated in GCA patients and cell lines, and their expression was associated with TNM stage and lymph node metastasis. Overexpression of MEG3 and miR-770 inhibited gastric cancer cell proliferation and invasion in vitro. Furthermore, the expression level of MEG3 and miR-770 was significantly increased in cancer cells after treated with 5-Aza-dC. The aberrant hypermethylation of proximal promoter and enhancer region of MEG3 was detected in GCA tissues. In addition, the proximal promoter and enhancer region hypermethylation and dysregulation of MEG3 and miR-770 were associated with poorer GCA patients' survival. These findings suggest that miR-770 and its host gene MEG3 may play tumor suppressor role and hypermethylation of proximal promoter and enhancer region may be one of the critical mechanisms in inactivation of MEG3 and miR-770 in GCA development. MEG3 and miR-770 may be used as potential biomarkers in predicting GCA patients' prognosis.
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Special Care Hospital of Hebei Province, Shijiazhuang, Hebei, China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Kuang
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Supeng
authors.initials: S
authors.lastname: Shen
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002299:Cardia / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C498907:MEG3 non-coding RNA, human; C000609533:MIRN-770 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding
keywords: MEG3; expression; gastric cardia adenocarcinoma; methylation; miR-770