Dataset Information

Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.

ABSTRACT:

Background

Radiotherapy plays an important role in cancer therapy. However, the radioresistance of some human cancers, particularly renal carcinoma, often results in radiotherapy failure. The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells, but effect of Ku70 expression on radiosensitivity in renal carcinoma is unclear. Here, we investigate the impact of Ku70 on radiosensitivity in renal carcinoma cells through regulating the expression of Ku70.

Methods

The stable overexpression of Ku70 or suppression of Ku70 in renal carcinoma cell line (786-O) was generated by retrovirus-mediated Ku70 cDNA or shRNA targeting Ku70. Ku70 expression was determined by RT-PCR and Western blot analysis, the apoptosis of the stable cells was assayed with flow cytometry and TUNEL assay and the effect of radiation on the livability of stable cells was assessed by MTT assay.

Results

Up-regulation of Ku70 expression of 786-O cells could inhibit cell apoptosis and reduce susceptibility to radiation. On the contrary, 786-O cells with suppression of Ku70 expression could induce cell apoptosis and significantly enhance the sensitivity to radiation.

Conclusions

These findings indicated that Ku70 might play an important role in radioresistance of renal carcinoma, and inhibition of Ku70 can increase the radiosensitivity of 786-O cells by enhancing apoptosis, suggesting down-regulation of Ku70 expression combined with radiotherapy will be a potential strategy for renal cell carcinoma therapy.

SUBMITTER: Qi D

PROVIDER: S-EPMC4047436 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.

Qi Defeng D Hu Yuan Y Zhang Yangde Y Peng Tao T Ji Weidong W

Cancer cell international 20140526

<h4>Background</h4>Radiotherapy plays an important role in cancer therapy. However, the radioresistance of some human cancers, particularly renal carcinoma, often results in radiotherapy failure. The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells, but effect of Ku70 expression on radiosensitivity in renal carcinoma is unclear. Here, we investigate the impact of Ku70 on radiosensitivity in renal carcinoma cells through regulating the expression ...[more]

PMID: 24910538

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Project description:BackgroundB cell translocation gene 1 (BTG1) has long been recognized as a tumor suppressor gene. Recent reports demonstrated that BTG1 plays an important role in progression of cell cycle and is involved in cellular response to stressors. However, the microRNAs mediated regulatory mechanism of BTG1 expression has not been reported so far. MicroRNAs can effectively influence tumor radiosensitivity by preventing cell cycle progression, resulting in enhancement of the cytotoxicity of radiotherapy efficacy. This study aimed to demonstrating the effects of microRNAs on the BTG1 expression and cellular radiosensitivity.MethodsThe human renal carcinoma 786-O cells were treated with 5 Gy of X-rays. Expressions of BTG1 gene and miR-454-3p, which was predicted to target BTG1 by software algorithm, were analyzed by quantitative polymerase chain reaction. Protein expressions were assessed by Western blot. Luciferase assays were used to quantify the interaction between BTG1 3'-untranslated region (3'-UTR) and miR-454-3p. The radiosensitivity was quantified by the assay of cell viability, colony formation and caspase-3 activity.ResultsThe expression of the BTG1 gene in 786-O cells was significantly elevated after treatments with X-ray irradiation, DMSO, or serum starvation. The up-regulation of BTG1 after irradiation reduced cellular radiosensitivity as demonstrated by the enhanced cell viability and colony formation, as well as the repressed caspase-3 activity. In comparison, knock down of BTG1 by siRNA led to significantly enhanced cellular radiosensitivity. It was found that miR-454-3p can regulate the expression of BTG1 through a direct interaction with the 3'-UTR of BTG1 mRNA. Decreasing of its expression level correlates well with BTG1 up-regulation during X-ray irradiation. Particularly, we observed that over-expression of miR-454-3p by transfection inhibited the BTG1 expression and enhanced the radiosensitivity. In addition, cell cycle analysis showed that over-expression of miR-454-3p shifted the cell cycle arrest from G2/M phase to S phase.ConclusionsOur results indicate that BTG1 is a direct target of miR-454-3p. Down-regulation of BTG1 by miR-454-3p renders tumor cells sensitive to radiation. These results may shed light on the potential application in tumor radiotherapy.

Dataset Information

Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.

Background

Methods

Results

Conclusions

Publications

Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.

Similar Datasets

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