Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/1748-717X-9-179) contains supplementary material, which is available to authorized users.
Highlights
B cell translocation gene 1 (BTG1) has long been recognized as a tumor suppressor gene
To investigate whether BTG1 functions as a responder to ionizing radiation (IR), we examined the protein levels of BTG1 in response to 5 Gy of X-rays in renal carcinoma 786-O cells by Western blot analysis
Tumor cell sensitivity to IR correlates with BTG1 levels Because BTG1 is involved in the regulation of cell cycle progression and responds to IR, we examined the effects of BTG1 expression on the radiosensitivity of renal carcinoma 786-O cells
Summary
B 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. This study aimed to demonstrating the effects of microRNAs on the BTG1 expression and cellular radiosensitivity. Tumor suppressor genes that regulate cell cycle can alter the radiosensitivity of cancer cells. Some studies have shown that BTG1 is involved in the general processes of cell cycle control and in cellular responses to stress [15], though a specific role for BTG1 in renal cell carcinoma has not been determined. In consideration of the common physiological function of tumor suppressor genes in controlling cell cycle, we propose that BTG1 may have a similar impact as RB1, p53, and p21 on the radiosensitivity of renal carcinoma tumor cells
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