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microRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer

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Abstract

MicroRNA-124 (miR-124), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as tumor suppressor microRNA. In this study, we found that miR-124 was down-regulated in gastric cancer cell lines and specimens. Restoration of miR-124 expression inhibited the proliferation and colony formation of gastric cancer cells. EZH2 (enhancer of zeste homolog 2), which has been shown to be an important transcription factor involved in the proliferation and metastasis of tumor cells, was here confirmed to be a direct target gene of miR-124. On the other hand, silencing EZH2 also inhibits cell proliferation of gastric cancer cells. Furthermore, the treatment combining miR-124 with 5-fluorouracil (5-FU) significantly showed more efficient anti-tumor effects than single treatment of miR-124 or 5-FU, and over-expression of miR-124 suppresses the tumor growth in vivo. Our study indicate that miR-124 can suppress gastric cancer cell growth by directly targeting the EZH2 gene and sensitize the treatment effect of 5-FU. Therefore, miR-124 shows tumor-suppressive activity and may be a new and useful approach of gastric cancer therapy.

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Acknowledgments

This study was supported by the Nature Scientific Foundation of China (81172575, 31100935, 81101643).

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Authors and Affiliations

  1. Cancer Research Institute, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, 28 West Changsheng Road, Hengyang, Hunan, 421001, People’s Republic of China

    Liming Xie, Zhiwei Zhang, Xi Zeng, Yuanjie Xie, Suyun Li, Guohua Tang & Xiusheng He

  2. Center for Gastric Cancer Research of Human Province, The First Affiliated Hospital, University of South China, Hengyang, Hunan, People’s Republic of China

    Liming Xie, Zhiqin Tan & Rongfang He

  3. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 East Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China

    Hailin Tang

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  1. Liming Xie
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Correspondence to Hailin Tang or Xiusheng He.

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Liming Xie and Zhiwei Zhang have contributed equally to this work.

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Xie, L., Zhang, Z., Tan, Z. et al. microRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer. Mol Cell Biochem 392, 153–159 (2014). https://doi.org/10.1007/s11010-014-2028-0

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