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A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma

Oncogene volume 32, pages 3432–3442 (2013)Cite this article

Abstract

Aberrant expression and altered function of transcription factors (TFs) have vital roles in many aspects of tumor development and progression. In this study, we investigated the functional significance of a TF, Yin Yang1 (YY1) in tumorigenesis of endometrioid endometrial carcinoma (EEC). We demonstrated that YY1 is upregulated in EEC cell lines and primary tumors; and its expression is associated with tumor stages. Depletion of YY1 inhibits EEC cell proliferation and migration both in vitro and in vivo, whereas overexpression of YY1 promotes EEC cell growth. These results suggest that YY1 functions as an oncogenic factor in EEC. Transcriptome analysis revealed a significant effect of YY1 on critical aspects of EEC tumorigenesis through inhibition of APC expression. Further mechanistic investigation uncovered a new epigenetic silencing mode of APC by YY1 through recruitment of EZH2 and trimethylation of histone 3 lysine 27 on its promoter region. Moreover, YY1 overexpression was found to be a consequence of miR-193a-5p downregulation through direct miR-193a-5p-YY1 interplay. Our results therefore establish a novel miR-193a-5p-YY1-APC axis, which contributes to EEC development, and may serve as future intervention target.

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Acknowledgements

The work described in this paper was substantially supported by three General Research Funds (GRFs) from Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (CUHK476309 and CUHK476310 to HW, and CUHK473211 to HS), and three CUHK direct grants (2041474 to HS and 2041492 and 2041662 to HW).

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, SAR, China

    Y Yang, L Zhou, L Wang, L K Y Chan, T Zhang, J Kwong, T H Cheung, T Chung & H Wang

  2. Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China

    Y Yang, L Zhou, L Lu, L Wang, X Li, P Jiang, L K Y Chan, T Zhang, J Yu, J Kwong, H Sun & H Wang

  3. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, China

    L Lu, P Jiang & H Sun

  4. Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China

    X Li & J Yu

  5. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China

    K Mak

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Correspondence to H Wang.

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Yang, Y., Zhou, L., Lu, L. et al. A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma. Oncogene 32, 3432–3442 (2013). https://doi.org/10.1038/onc.2012.360

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  • DOI: https://doi.org/10.1038/onc.2012.360

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