miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

  • Authors:
    • Jacqueline Keßler
    • Swetlana Rot
    • Matthias Bache
    • Matthias Kappler
    • Peter Würl
    • Dirk Vordermark
    • Helge Taubert
    • Thomas Greither
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  • Published online on: October 26, 2016     https://doi.org/10.3892/ol.2016.5320
  • Pages: 5281-5288
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Abstract

Soft tissue sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin. Partly due to hypoxia, an aggressive and radioresistant phenotype frequently develops, resulting in poorer patient outcome. microRNAs (miRNAs) are tiny, non-coding regulators of gene expression and in situations of cellular stress situations may predict clinical progression and patient outcome. In the present study, hypoxia‑associated miR‑199a‑5p expression in 96 soft tissue sarcoma samples was analysed by reverse transcription‑quantitative polymerase chain reaction and associations between miR-199a-5p expression and patient clinicopathological characteristics and survival were measured. Additionally, luciferase reporter assays analyzed the post‑transcriptional regulation of hypoxia‑associated genes hypoxia‑inducible factor 1α (HIF‑1α), oxidative stress induced growth inhibitor 2 (OSGIN2) and vascular endothelial growth factor (VEGF) by miR‑199a‑5p. Survival analyses indicated that low expression of miR‑199a‑5p was significantly correlated with poorer tumor‑specific survival (univariate Cox's‑Regression analyses; relative risk=1.92, P=0.029). Furthermore, it was demonstrated that the 3'UTR of HIF‑1α and OSGIN2 genes were regulated by miR‑199a‑5p in‑vitro, although the 3'UTR of VEGF was not. To the best of our knowledge, this is the first report demonstrating the regulation of the 3'untranslated region of the OSGIN2 gene by miR-199a-5p and a significant correlation between low miR‑199a‑5p expression and a poor outcome of patients with soft tissue sarcoma.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Keßler J, Rot S, Bache M, Kappler M, Würl P, Vordermark D, Taubert H and Greither T: miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome. Oncol Lett 12: 5281-5288, 2016
APA
Keßler, J., Rot, S., Bache, M., Kappler, M., Würl, P., Vordermark, D. ... Greither, T. (2016). miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome. Oncology Letters, 12, 5281-5288. https://doi.org/10.3892/ol.2016.5320
MLA
Keßler, J., Rot, S., Bache, M., Kappler, M., Würl, P., Vordermark, D., Taubert, H., Greither, T."miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome". Oncology Letters 12.6 (2016): 5281-5288.
Chicago
Keßler, J., Rot, S., Bache, M., Kappler, M., Würl, P., Vordermark, D., Taubert, H., Greither, T."miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome". Oncology Letters 12, no. 6 (2016): 5281-5288. https://doi.org/10.3892/ol.2016.5320