Knockdown of hnRNPK leads to increased DNA damage after irradiation and reduces survival of tumor cells

Radiotherapy is an important treatment option in the therapy of multiple tumor entities among them head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by the development of radiation resistances. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofac...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2017-03, Vol.38 (3), p.321-328
Main Authors: Wiesmann, Nadine, Strozynski, Judith, Beck, Carina, Zimmermann, Nadine, Mendler, Simone, Gieringer, Rita, Schmidtmann, Irene, Brieger, Jürgen
Format: Article
Language:English
Subjects:
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - radiotherapy
Cell Line, Tumor
Cell Survival - radiation effects
DNA Damage - radiation effects
Gene Knockdown Techniques
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - pathology
Head and Neck Neoplasms - radiotherapy
Heterogeneous-Nuclear Ribonucleoprotein K - genetics
Histones - genetics
Humans
Radiation Tolerance - genetics
Radiation Tolerance - radiation effects
Squamous Cell Carcinoma of Head and Neck
Stem Cells - radiation effects
Tumor Suppressor Protein p53 - genetics
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Summary:Radiotherapy is an important treatment option in the therapy of multiple tumor entities among them head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by the development of radiation resistances. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and represents a potential target for radio sensitization of tumor cells. In this study, we analyzed the impact of hnRNPK on the DNA damage response after gamma irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA damage levels in irradiated cells. Tumor cells bearing a p53 mutation showed increased damage levels and delayed repair. Knockdown of hnRNPK applied simultaneously with irradiation reduced colony-forming ability and survival of tumor cells. Taken together, our data shows that hnRNPK is a relevant modifier of DNA damage repair and tumor cell survival. We therefore recommend further studies to evaluate the potential of hnRNPK as a drug target for improvement of radiotherapy success.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgx006