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miR-124 functions as a tumor suppressor in the endometrial carcinoma cell line HEC-1B partly by suppressing STAT3

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Abstract

MicroRNAs (miRNAs) play an important role in the development and progression of endometrial carcinoma (EC). Recently, several studies have shown that microRNA-124 (miR-124) is downregulated in various cancers, which can affect tumor initiation and maintenance. However, the effects of miR-124 on EC are largely unknown. In this study, we identified the under-expression of miR-124 in 35 paired EC tissues and adjacent normal tissues. Further, functional experiments found that ectopic expression of miR-124 markedly suppressed cell proliferation, migration, and invasion of EC cells. It also induced cell apoptosis and G1-phase cell cycle arrest. Moreover, we identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124, and over expression of miR-124 not only induced changes in STAT3 expression but also altered expression of its target genes, cyclin D2 and matrix metalloproteinase 2, in the human endometrial carcinoma cell line HEC-1B. In addition to targeting STAT3 directly, we found that miR-124 suppresses phosphorylation of STAT3 through targeting IL-6R indirectly. Restored STAT3 expression through treatment with IL-6 cytokine partly abolished miR-124-mediated cell cycle arrest and apoptosis induction. These results combined with the tumorigenetic role of STAT3 in HEC-1B cells suggest that the antitumor effects of miR-124 are achieved, at least partly, through down regulation of STAT3 mRNA and its downstream target genes. Therefore, inhibition of constitutively activated STAT3 by ectopic expression of miR-124 in EC may provide a novel therapeutic strategy for the treatment of EC.

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Acknowledgments

The authors thank Fang Wang for technical assistance and valuable discussion of the manuscript. This work was supported by grants from the National Natural Science Foundation of China (81260033/H0204), the Jiangxi Provincial Science & Technology Commission (20121BBG70054), and the Provincial Natural Science Foundation (20122BAB205023).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Yunyun Li, Xiuxia Liu & Qing Cao

  2. Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Zhongzu Zhang

  3. The Key Laboratory of Molecular Medicine of Jiangxi Province, Nanchang, 330006, Jiangxi, People’s Republic of China

    Xiuxia Liu, Wenfeng He, Yang Shen, Xin Liu, Kui Hong & Qing Cao

  4. The Cardiovascular Systemetic Key Laboratory of Jiangxi Province, Nanchang, 330006, Jiangxi, People’s Republic of China

    Xiuxia Liu, Wenfeng He, Yang Shen, Xin Liu, Kui Hong & Qing Cao

  5. Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, Jiangxi, People’s Republic of China

    Tingting Huang

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  1. Yunyun Li
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  2. Zhongzu Zhang
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  7. Xin Liu
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  9. Qing Cao
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Correspondence to Qing Cao.

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Yunyun Li and Zhongzu Zhang contributed equally to this work.

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Li, Y., Zhang, Z., Liu, X. et al. miR-124 functions as a tumor suppressor in the endometrial carcinoma cell line HEC-1B partly by suppressing STAT3. Mol Cell Biochem 388, 219–231 (2014). https://doi.org/10.1007/s11010-013-1913-2

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  • DOI: https://doi.org/10.1007/s11010-013-1913-2

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