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Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma

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Abstract

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC-823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients’ survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis.

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Acknowledgments

We thank the patients for taking part in this study. Supported by Grants from the National Natural Science Foundation (No. 81472335), Natural Science Foundation of Hebei Province (No. H2015206196), and Grants from the Ordinary University Considerable Distinctive Subjects Foundation of Hebei Province (No. 200552).

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    Authors and Affiliations

    1. Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

      Wei Guo, Zhiming Dong, Yabin Shi, Shengnan Liu, Jia Liang, Yanli Guo, Xin Guo & Supeng Shen

    2. Surgery Department, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, 050011, Hebei, China

      Guiying Wang

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    1. Wei Guo
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    Correspondence to Guiying Wang.

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    Wei Guo and Zhiming Dong contributed equally to this work.

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    Guo, W., Dong, Z., Shi, Y. et al. Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma. Clin Exp Metastasis 33, 497–508 (2016). https://doi.org/10.1007/s10585-016-9794-x

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