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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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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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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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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).

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