Silencing of XRCC4 increases radiosensitivity of triple-negative breast cancer cells

Autor: Shuguang Zuo, Kanda Fu, Liping Wang, Yuqing Wen, Gongpeng Dai
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
DNA Repair
medicine.medical_treatment
Biophysics
Triple Negative Breast Neoplasms
Biology
Biochemistry
Radiation Tolerance
Small hairpin RNA
03 medical and health sciences
0302 clinical medicine
RNA interference
Cell Line
Tumor
Radiation
Ionizing
medicine
Humans
MTT assay
DNA Breaks
Double-Stranded
Radiosensitivity
Molecular Biology
Triple-negative breast cancer
Research Articles
Aged
Cell Proliferation
Gene knockdown
Cell Biology
DNA repair protein XRCC4
Middle Aged
Progression-Free Survival
Comet assay
Radiation therapy
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
030104 developmental biology
X-ray repaircross complementing protein 4
radiosensitivity
030220 oncology & carcinogenesis
triple negative breast cancer
Cancer research
Female
Comet Assay
Research Article
Zdroj: Bioscience Reports
ISSN: 1573-4935
Popis: Background: Radiotherapy is an important locoregional treatment, and its effect on triple-negative breast cancer (TNBC) needs to be enhanced. The aim of the present study was to investigate the potential effects of XRCC4 on radiosensitivity of TNBC. Methods: The RNAi technique was implemented to establish the TNBC stable cell line with XRCC4 knockdown. MTT assay was used to detect the effect of XRCC4 knockdown on cell proliferation. Western blot and immunohistochemistry assays were employed to identify protein expression. Colony assay was performed to detect the effect of XRCC4 knockdown on the colony formation ability of TNBC cells with radiation treatment. Comet assay was conducted to evaluate the influence of XRCC4 silencing on DNA repair activity in ionizing radiation. In addition, we performed a survival analysis based on data in TCGA database. Results: XRCC4 knockdown by lentivirus-mediated shRNA had no significant effect on proliferation of TNBC cells. Knockdown of XRCC4 could substantially increase the sensitivity of TNBC cells to ionizing radiation. The DNA damage level was detected to be increased in the XRCC4 knockdown group, indicating there was a significant repair delay in the XRCC4-deleted cells. Clinical sample analysis exhibited that there were various XRCC4 expression in different patients with TNBC. Moreover, survival analysis showed that high expression of XRCC4 was significantly associated with poor progression-free survival after radiotherapy in TNBC patients. Conclusion: Our findings suggest that XRCC4 knockdown sensitizes TNBC cells to ionizing radiation, and could be considered as a novel predictor of radiosensitivity and a promising target for TNBC.
Databáze: OpenAIRE
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