Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells

doi:10.1186/1748-717X-9-179

	Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells
	Wu,Xin 1,2; Ding,Nan 2; Hu,Wentao 2; He,Jinpeng 1,2; Xu,Shuai 1,2; Pei,Hailong 1,2; Hua,Junrui 2; Zhou,Guangming 2; Wang,Jufang 2
刊名	Radiation Oncology
	2014-08-12
卷号	9 期号:1
关键词	microRNA BTG1 miR-454-3p Radiosensitivity S phase arrest
ISSN号	1748-717X
DOI	10.1186/1748-717X-9-179
英文摘要	AbstractBackgroundB 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.
资助项目	National Natural Science Foundations of China[U1232125] ; National Natural Science Foundations of China[31270895] ; National Natural Science Foundations of China[11335011] ; National Natural Science Foundations of China[31370846]
WOS关键词	RADIATION SENSITIVITY ; INDUCED APOPTOSIS ; PROTEIN BTG1 ; EXPRESSION ; GENE ; CANCER ; PROLIFERATION ; LEUKEMIA ; TARGETS ; MIR-21
WOS研究方向	Oncology ; Radiology, Nuclear Medicine & Medical Imaging
语种	英语
出版者	BioMed Central
WOS记录号	BMC:10.1186/1748-717X-9-179
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/24460]
专题	中国科学院近代物理研究所
通讯作者	Wang,Jufang
作者单位	1.University of Chinese Academy of Sciences 2.Key Laboratory of Heavy Ion Radiation Biology and Medicine Institute of Modern Physics Chinese Academy of Sciences; Department of Space Radiobiology
推荐引用方式 GB/T 7714	Wu,Xin,Ding,Nan,Hu,Wentao,et al. Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells[J]. Radiation Oncology,2014,9(1).
APA	Wu,Xin.,Ding,Nan.,Hu,Wentao.,He,Jinpeng.,Xu,Shuai.,...&Wang,Jufang.(2014).Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells.Radiation Oncology,9(1).
MLA	Wu,Xin,et al."Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells".Radiation Oncology 9.1(2014).