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Wilke, C. ; Hess J. ; Klymenko, S.V.* ; Chumak, V.V.* ; Zakhartseva, L.M.* ; Bakhanova, E.V.* ; Feuchtinger, A. ; Walch, A.K. ; Selmansberger, M. ; Braselmann, H. ; Schneider, L. ; Pitea, A. ; Steinhilber, J.* ; Fend, F.* ; Bösmüller, H.C.* ; Zitzelsberger, H. ; Unger, K.

Expression of miRNA-26b-5p and its target TRPS1 is associated with radiation exposure in post-Chernobyl breast cancer.

Int. J. Cancer 142, 573-583 (2018)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
Ionising radiation is a well-recognised risk factor for the development of breast cancer, however, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and non-exposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n=38) were subsequently validated in a second cohort (n=39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p was associated with radiation exposure. Since TRPS1 overexpression is common in sporadic breast cancer its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterised in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, whilst the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chernobyl ; Trps1 ; Breast Cancer ; Hsa-mir-26b-5p ; Radiation-associated; Mesenchymal Transition; Dna-damage; Cell-cycle; Gene; Microrna; Promotes; Progression; Biomarkers; Cytoscape; Apoptosis
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Zeitschrift International Journal of Cancer
Quellenangaben Band: 142, Heft: 3, Seiten: 573-583 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (TMO)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Analytical Pathology (AAP)