The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

    1. Jan J Brosens2
    1. 1Cancer Research-UK Laboratories, Division of Cancer and
      2Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    1. (Correspondence should be addressed to E W-F Lam; Email: eric.lam{at}


    The rise and fall in ovarian oestrogen and progesterone production orchestrates a series of events that are indispensable for reproduction, including ovulation, implantation, decidualisation and menstruation. In the uterus, these events involve extensive tissue remodelling, characterised by waves of endometrial cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown, menstruation and regeneration. The ability of ovarian hormones to trigger such diverse physiological responses is foremost dependent upon interaction of activated steroid receptors with specific transcription factors, such as Forkhead box class O (FOXO) proteins, involved in cell fate decisions. Furthermore, micro-RNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, have emerged as a major regulator system of steroid hormone responses in the female reproductive tract. Consequently, increasing evidence shows that deregulated uterine miRNA expression underpins a spectrum of common reproductive disorders, ranging from implantation failure to endometriosis. Furthermore, by targeting FOXO transcription factors and other key regulators of tissue homeostasis, oncogenic endometrial miRNAs promote tumourigenesis and cancer progression.

    • Received in final form 25 January 2011
    • Accepted 7 March 2011
    • Made available online as an Accepted Preprint 7 March 2011
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