Open Access

Glucocorticoid receptor overexpression slightly shifts microRNA expression patterns in triple-negative breast cancer

  • Authors:
    • Dominik Buschmann
    • Ricardo González
    • Benedikt Kirchner
    • Claudia Mazzone
    • Michael W. Pfaffl
    • Gustav Schelling
    • Ortrud Steinlein
    • Marlene Reithmair
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  • Published online on: March 27, 2018     https://doi.org/10.3892/ijo.2018.4336
  • Pages: 1765-1776
  • Copyright: © Buschmann et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with limited options for clinical intervention. As with many solid tumors, TNBC is known to promote invasiveness and metastasis by secreting extracellular vesicles (EVs) capable of modulating the behaviour of recipient cells. Recent investigations have demonstrated that high expression levels of glucocorticoid receptor (GR) in TNBC are linked to therapy resistance, higher recurrence rates and increased mortality. In addition to activating protein-coding genes, GR is also involved in the expression of short non-coding RNAs including microRNAs (miRNAs or miRs). The molecular mechanisms responsible for the oncogenic effects of GR on TNBC have yet to be fully elucidated; however, emerging evidence suggests that miRNAs may play a pivotal role in tumorigenesis and metastasis. Thus, the aim of this study was to identify GR-regulated cellular and vesicular miRNAs that might contribute to the particularly oncogenic phenotype of TNBC with a high GR expression. We analyzed miRNA profiles of three TNBC cell lines using an in vitro model of GR overexpression. Next-generation sequencing revealed minor, cell line-specific changes in cellular miRNA expression, whereas vesicular miRNAs were not significantly regulated by GR. Additionally, the analysis of predicted miRNA targets failed to establish a causal link between GR-induced miRNA expression and oncogenic signaling. On the whole, given that GR influences miRNA profiles to only a small degree, other mechanisms are more likely to be responsible for the increased mortality of patients with TNBC with a high GR expression.
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June 2018
Volume 52 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Buschmann, D., González, R., Kirchner, B., Mazzone, C., Pfaffl, M.W., Schelling, G. ... Reithmair, M. (2018). Glucocorticoid receptor overexpression slightly shifts microRNA expression patterns in triple-negative breast cancer. International Journal of Oncology, 52, 1765-1776. https://doi.org/10.3892/ijo.2018.4336
MLA
Buschmann, D., González, R., Kirchner, B., Mazzone, C., Pfaffl, M. W., Schelling, G., Steinlein, O., Reithmair, M."Glucocorticoid receptor overexpression slightly shifts microRNA expression patterns in triple-negative breast cancer". International Journal of Oncology 52.6 (2018): 1765-1776.
Chicago
Buschmann, D., González, R., Kirchner, B., Mazzone, C., Pfaffl, M. W., Schelling, G., Steinlein, O., Reithmair, M."Glucocorticoid receptor overexpression slightly shifts microRNA expression patterns in triple-negative breast cancer". International Journal of Oncology 52, no. 6 (2018): 1765-1776. https://doi.org/10.3892/ijo.2018.4336