Poster Presentation 25th Lorne Cancer Conference 2013

Cis-regulation of non-codings RNAs within the HOXC locus in breast cancer (#279)

Michael Milevskiy 1 , Peter Bailey 1 , Stacey Edwards 1 , Juliet French 1 , Melissa Brown 1
  1. The School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD, Australia

The HOXC locus on human chromosome 12 encodes a number of coding and non-coding genes that are strongly implicated in development and cancer.  The Non-coding RNA (ncRNA) HOTAIR for example, has prognostic value for both metastasis and survival in breast cancer, and HOTAIR, miR-196a and miR-615 have been shown to influence metastasis through downstream regulation of tumour suppressors and oncogenes in vitro1 . Characterisation of cis-regulatory elements within and flanking this region has led to the identification of a putative enhancer that physically loops to several regions throughout the HOXC locus2 . This cis-regulatory element fell within a region devoid of genes over 100kb upstream of the locus. The putative enhancer demonstrated selective potentiation of the HOTAIR promoter in a luciferase reporter assay. Bioinformatic analysis predicts hormone receptors and their cofactors are important in the regulation of these ncRNAs, through both promoter and enhancer binding. We are currently in the process of deciphering the role of these factors through hormone treatment, overexpression and knockdown experiments in tissue culture. It is hoped that the factors regulating the expression of HOXC ncRNAs will have prognostic value for breast cancers in particular for predicting their potential for metastasis.

  1. Gupta and Chang. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010
  2. Fullwood and Ruan. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 2009