MicroRNA-19b 通过下调 BTG1 增加重离子辐射诱导的基因组不稳定性

Abstract

重离子束放疗可有效杀死肿瘤细胞。研究表明：重离子束能引起癌细胞的基因异常，引发基因组不稳定性。BTG1作为一个重要的G0/G1 期相关蛋白，具有强烈的抗细胞增殖能力。以碳离子辐射为手段，通过蛋白质印迹杂交技术发现：人肾癌786-O 细胞中BTG1 能够对重离子辐射应激产生应答。同时，荧光定量PCR结果显示碳离子辐照后，BTG1转录本与microRNA-19b 的表达水平呈负相关变化。瞬时转染microRNA-19b 类似物于人肾癌786-O 细胞中，能够抑制由碳离子辐射引起的BTG1 蛋白上调，并增加细胞的微核发生率。因此microRNA-19b 能够通过抑制BTG1 的表达，增加重离子辐射诱导的细胞基因组不稳定性。 Heavy ion radiotherapy is a curative treatment for human malignancies and offers hopeful prospects for the treatment of cancer. Recent studies demonstrate that heavy ion irradiation leads to not only cell killing but also genomic instability. Expression of BTG1 inhibits the proliferation of cells and plays important roles in the progress from G0/G1 to S phase in cell cycle. In this study, we found that BTG1 was inducible in human renal cancer 786-O cells in the presence of carbon ion irradiation. Meanwhile, the results of qRT-PCR analyses displayed an inverse relationship between expression of BTG1 and microRNA-19b at different times. The up-regulation of BTG1, which was induced by carbon ion irradiation, was inhibited by microRNA-19b mimic transfected into 786-O cells. Subsequently, down-regulation of BTG1 increased the number of micronuclei in bi-nucleated cell of 786-O cells. Thus, we speculate that microRNA-19b leads to enhancement of heavy ion irradiation induced genomic instability by inhibiting the expression of BTG1 gene.