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

Eric W.‐F. Lam, Eric W-F Lam, Kunal Shah, Shah K, Jan J. Brosens
The Journal of endocrinology · 2011 · vol. 212(1) , pp. 13–25 · doi:10.1530/joe-10-0480 · PMID:21382987 · W2155764306
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Micro-RNAs and FOXO transcription factors regulate sex steroid hormone actions in the cycling endometrium and are implicated in endometrial cancer progression by targeting key tissue homeostasis regulators.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Endometrial Neoplasms Endometrium Forkhead Transcription Factors Gonadal Steroid Hormones MicroRNAs Animals Animals Biomarkers Biomarkers Biomarkers Cell Transformation, Neoplastic Cell Transformation, Neoplastic Endometrial Neoplasms Endometrial Neoplasms Endometrium Endometrium Female Female Forkhead Transcription Factors Forkhead Transcription Factors

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