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Aberrant methylation-mediated silencing of lncRNA CTC-276P9.1 is associated with malignant progression of esophageal squamous cell carcinoma

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Abstract

Downregulation and aberrant hypermethylation of long non-coding RNA CTC-276P9.1 have been detected in limited tumors. However, the distribution of methylated CpG sites and biological role of CTC-276P9.1 in esophageal squamous cell carcinoma (ESCC) progression and prognosis have not been fully clarified. The present study was to investigate the expression status and the distribution of methylated CpG sites within the three CpG islands of CTC-276P9.1, further to clarify its functional role and prognostic value in ESCC development and prognosis. Significant downregulation of CTC-276P9.1 was detected in esophageal cancer cells and ESCC tissues, and the expression of CTC-276P9.1 in ESCC tissues was associated with TNM stage, pathological differentiation, lymph node metastasis, and distant metastasis or recurrence. The expression level of CTC-276P9.1 in esophageal cancer cells was significantly reversed by treatment with 5-Aza-dC and TSA. The aberrant hypermethylation of the regions around the transcription start site was more tumor specific and associated with the expression levels of CTC-276P9.1. Moreover, histone modification may also participate in the regulation of CTC-276P9.1. Furthermore, over-expression of CTC-276P9.1 inhibited esophageal cancer cells proliferation and invasion in vitro, decreased the expression of proliferative markers and inhibited esophageal cancer cells invasion probably by regulating EMT. In addition, the dysregulation and hypermethylation of the regions around the transcription start site of CTC-276P9.1 were associated with poorer ESCC patients’ survival. These findings suggest that CTC-276P9.1 may act as a tumor suppressor and may be employed as a new prognostic factor and therapeutic target for ESCC.

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Acknowledgements

We thank the cases for taking part in this study. This study was supported by Grants from the National Natural Science Foundation of China (Nos. 81472335 and 81572441), Natural Science Foundation of Hebei Province (Nos. H2015206196 and H2015206420).

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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, Shengnan Liu, Zhiming Dong, Yanli Guo, Chunyan Ding, Supeng Shen & Jia Liang

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

      Baoen Shan

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    1. Wei Guo
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    Correspondence to Baoen Shan.

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    Wei Guo, Shengnan Liu, and Zhiming Dong have contributed equally to this work.

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    Guo, W., Liu, S., Dong, Z. et al. Aberrant methylation-mediated silencing of lncRNA CTC-276P9.1 is associated with malignant progression of esophageal squamous cell carcinoma. Clin Exp Metastasis 35, 53–68 (2018). https://doi.org/10.1007/s10585-018-9881-2

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