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Downregulation and aberrant hypermethylation of C5orf66\u2010AS1 have been detected in a limited several tumors. However, the biological role and distribution of methylated CpG sites of C5orf66\u2010AS1 in gastric cardia adenocarcinoma (GCA) development and prognosis are poorly clarified. The present study was to investigate the expression status and function of C5orf66\u2010AS1 in GCA, and to detect the distribution of methylated CpG sites within the three CpG islands of the promoter and gene body of C5orf66\u2010AS1, further to clarify its prognostic value in GCA patients. C5orf66\u2010AS1 was significantly downregulated in GCA tissues and cell lines, and the expression level was associated with TNM stage, pathological differentiation, lymph node metastasis, and distant metastasis or recurrence. The expression level of C5orf66\u2010AS1 was significantly increased in cancer cells after treated with 5\u2010Aza\u2010dC. Further methylation analysis demonstrated that the aberrant hypermethylation of the regions around the transcription start site of C5orf66\u2010AS1 was more tumor specific and was associated with its expression. Moreover, Sp1 may upregulate C5orf66\u2010AS1 expression and CpG sites hypermethylation within the binding sites may abrogate Sp1 binding. In addition, C5orf66\u2010AS1 inhibited gastric cancer cell proliferation and invasion, and the dysregulation and hypermethylation of the regions around the transcription start site of C5orf66\u2010AS1 were associated with poorer GCA patients\u2019 survival. These findings suggest that aberrant hypermethylation\u2010mediated downregulation of C5orf66\u2010AS1 may play important roles in GCA tumorigenesis and C5orf66\u2010AS1 may serve as a potential prognostic marker in predicting GCA patients\u2019 survival.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22806","type":"journal-article","created":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T19:21:49Z","timestamp":1521746509000},"page":"854-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aberrant methylation\u2010mediated downregulation of long noncoding RNA C5orf66\u2010AS1 promotes the development of gastric cardia adenocarcinoma"],"prefix":"10.1002","volume":"57","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"Laboratory of Pathology Hebei Cancer Institute The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei 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