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EZH2 elevates the proliferation of human cholangiocarcinoma cells through the downregulation of RUNX3

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Abstract

To investigate the impact of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on the proliferation and apoptosis of human cholangiocarcinoma cells as well as its related mechanisms. Immunohistochemistry and Western blot analyses were used to examine the expression of EZH2 in 40 cases of human cholangiocarcinoma tissues and four strains of human cholangiocarcinoma cells. The influence of EZH2 on cell growth and apoptosis were assessed by knockdown experiments, and a xenograft experiment in nude mice was performed to evaluate the impact of siEZH2 on the tumorigenicity of tumor cells. The correlation of EZH2, clinic pathological features and overall survival rates was also analyzed. EZH2 was highly expressed in human cholangiocarcinoma tissues and cells. Silencing of EZH2 could significantly reduce the methylation level of RUNX3 DNA in human cholangiocarcinoma cells and improve its protein expression as well as inhibit cell proliferation, induce apoptosis and slow down the growth of tumor in nude mice. In addition, the expression of EZH2 was associated with the tumor stage, lymph node positivity and poor prognoses. Overexpression of EZH2 can promote the proliferation of cholangiocarcinoma cells and inhibit their apoptosis. It is associated with poor prognoses in patients with cholangiocarcinoma. Therefore, EZH2 could be a potential clinical therapeutic target for the treatment of cholangiocarcinoma.

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Acknowledgments

This research was supported in part by the National Natural Science Foundation of China (Nos. 81360367, 81160066 and 30870719), Key Project of Science and Technology for Colleges and Universities in Guangxi (2013ZD046), Pharmaceutical Technology Special Project of the Health Department in Guangxi (GZPT13-45), Open Fund Project of Key Laboratory of Molecular Medicine in Liver Damage and Repair, Guangxi (QT2013025), Construction Project of Key Laboratory of Molecular Medicine in Liver Damage and Repair, Guangxi (SYS2013009) and Guangxi Distinguished Experts Special Fund Project, which is supported by the Guangxi culture of advancing academic and technical leaders with project funds.

Conflict of interest

We declare that we have no conflict of interest, and this manuscript is approved by all authors for publication.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People’s Republic of China

    Bo Tang, Fang Tang, Zhenran Wang & Songqing He

  2. Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China

    Bo Tang & Songqing He

  3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, People’s Republic of China

    Jian Du

  4. Department of Medical Oncology, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People’s Republic of China

    Yang Li

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  1. Bo Tang
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Correspondence to Songqing He.

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Bo Tang and Jian Du have contributed equally to this work.

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Tang, B., Du, J., Li, Y. et al. EZH2 elevates the proliferation of human cholangiocarcinoma cells through the downregulation of RUNX3. Med Oncol 31, 271 (2014). https://doi.org/10.1007/s12032-014-0271-6

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