孙宝胜,左雅芳,田琦,欧健,张国胜,刘江山,刘博宇,刘士新.MiR-92a及其靶抑癌基因BCL11b在辐射诱导小鼠胸腺淋巴瘤中的作用[J].中华放射医学与防护杂志,2013,33(2):135-137
MiR-92a及其靶抑癌基因BCL11b在辐射诱导小鼠胸腺淋巴瘤中的作用
The role of miR-92a and BCL11b in radiation induced thymic lymphoma in BALB/c mice
投稿时间:2012-08-10  
DOI:10.3760/cma.j.issn.0254-5098.2013.02.006
中文关键词:  电离辐射  胸腺淋巴瘤  BCL11b  miR-92a
英文关键词:Ionizing radiation  Thymic lymphoma  BCL11b  miR-92a
基金项目:吉林省自然科学基金(201111211)
作者单位E-mail
孙宝胜 130012 长春,吉林省肿瘤医院  
左雅芳 130012 长春,吉林省肿瘤医院  
田琦 130012 长春,吉林省肿瘤医院  
欧健 130012 长春,吉林省肿瘤医院  
张国胜 130012 长春,吉林省肿瘤医院  
刘江山 130012 长春,吉林省肿瘤医院  
刘博宇 130012 长春,吉林省肿瘤医院  
刘士新 130012 长春,吉林省肿瘤医院 liushixin1964@sina.com 
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中文摘要:
      目的 采用电离辐射诱导的小鼠胸腺淋巴瘤动物模型,检测抑癌基因BCL11b和miR-92a的表达变化,探讨miR-92a对BCL11b基因的调控作用。方法 BALB/c小鼠采用γ射线全身照射,单次照射剂量和剂量率分别为1.75 Gy和0.382 Gy/min,每周1次,连续照射4周,计算电离辐射诱导小鼠胸腺淋巴瘤发生率。采用实时定量PCR法检测miR-92a表达变化情况,Western blot方法检测BCL11b蛋白表达变化情况;将miR-92a 序列插入载体pcDNA-DEST-47中构建真核表达质粒;构建BCL11b 基因3'UTR-荧光素酶报告质粒,与pcDNA-DEST- miR- 92a质粒共转染至EL-4细胞,分析miR-92a对BCL11b表达的调控作用。结果 辐射诱导的BALB/c小鼠胸腺淋巴瘤的发生率为58.51%。胸腺淋巴瘤细胞中BCL11b表达下调,而miR-92a表达上调,两者之间存在显著的负相关(r=-0.827,P<0.05)。psiCHECK 2-BCL11b 和pcDNA-DEST-miR-92a两种质粒共转染组的荧光素酶表达明显低于单独转染的空载体和靶基因BCL11b组(t=3.42,P<0.05)。结论 电离辐射诱导的小鼠胸腺淋巴瘤中miR-92a与BCL11b表达的负相关,提示miR-92a可能参与了辐射诱发肿瘤中BCL11b蛋白表达的调控作用。
英文摘要:
      Objective To investigate the expression of miR-92a and BCL11b gene in radiation-induced thymic lymphoma in BALB/c mice, and the regulation of BCL11b by miR-92a. Methods BALB/c mice were irradiated with 1.75 Gy gamma rays with a dose rate of 0.382 Gy/min, 4 weeks in a row and once per week. 6 months after radiation, the incidence of the thymic lymphoma induced by ionizing radiation was checked and the mice were sacrificed. The thymuses of 6 typical mice with thymic lymphoma in the irradiated group and 6 mice in control group were taken for further detection. Real-time PCR were used to detect miR-92a expression. Western blot and FACS were employed to measure protein expression of BCL11b. The miR-92a sequence was inserted into pcDNA-DEST-47 plasmid to construct the eukaryotic expression vector (pcDNA-DEST-miR-92a) and to construct the BCL11b gene 3'UTR luciferase reporter plasmid (psiCHECK 2-BCL11b) at the same time. They were used to transfect EL-4 cells together for analysis of the regulation of miR-92a on the expression of BCL11b. Results The incidence of the thymic lymphoma induced by ionizing radiation was 58.51%. It was found that expression of the tumor suppressor gene BCL11b was down-regulated and expression of miR-92a was up-regulated in radiation induced thymic lymphoma tissue samples. There was an inverse correlation between BCL11b protein and miR-92a expression level among different tissue samples (r=-0.827, P<0.05). The expression of luciferase in the group transfected with pcDNA-DEST-miR-92a and psiCHECK 2-BCL11b plasmids was significantly lower than that in the group transfected with empty plasmid and BCL11b gene (t=3.42,P<0.05). Conclusions miR-92a maybe participate in radiation-induced carcinogenesis and regulate the expression of BCL11b gene.
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