Transcriptional changes induced by the tumor dormancy-associated microRNA-190.
Transcriptional changes induced by the tumor dormancy-associated microRNA-190.
复制标题
DOI：
10.4161/trns.25558
复制
发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Hlatky L
中科院分区：
文献类型：
--
作者：
Almog N;Briggs C;Beheshti A;Ma L;Wilkie KP;Rietman E;Hlatky L
肿瘤休眠是癌症进展中非常普遍的阶段。我们先前已经生成并表征了人体肿瘤休眠的体内实验模型，其中微肿瘤保持隐匿，直到它们自发地转变为快速肿瘤生长。我们发现，休眠的微肿瘤在从休眠到快速生长表型的转变过程中经历了稳定的microRNA（miRNA）转换，并报告了人类肿瘤休眠相关miRNA（DmiRs）的共识签名的鉴定。miRNA-190（miR-190）是所有分析的休眠肿瘤中上调最多的DmiR之一。miR-190的上调导致在其他快速生长的胶质母细胞瘤和骨肉瘤中延长肿瘤休眠。在这里，我们研究了癌细胞中miR-190表达诱导的转录变化，并显示了胶质母细胞瘤和骨肉瘤细胞中miR-190介导的转录重编程的相似模式。这些数据表明，miR-190介导的效应依赖于肿瘤细胞中广泛的分子变化网络，并且miR-190影响几种转录因子、肿瘤抑制基因和干扰素反应途径。这项工作中描述的肿瘤休眠的分子机制可能为癌症的早期预防提供有希望的靶点，并可能导致新的治疗方法，将恶性肿瘤表型转化为无症状的休眠状态。
Tumor dormancy is a highly prevalent stage in cancer progression. We have previously generated and characterized in vivo experimental models of human tumor dormancy in which micro-tumors remain occult until they spontaneously shift into rapid tumor growth. We showed that the dormant micro-tumors undergo a stable microRNA (miRNA) switch during their transition from dormancy to a fast-growing phenotype and reported the identification of a consensus signature of human tumor dormancy-associated miRNAs (DmiRs). miRNA-190 (miR-190) is among the most upregulated DmiRs in all dormant tumors analyzed. Upregulation of miR-190 led to prolonged tumor dormancy in otherwise fast-growing glioblastomas and osteosarcomas. Here we investigate the transcriptional changes induced by miR-190 expression in cancer cells and show similar patterns of miR-190 mediated transcriptional reprogramming in both glioblastoma and osteosarcoma cells. The data suggests that miR-190 mediated effects rely on an extensive network of molecular changes in tumor cells and that miR-190 affects several transcriptional factors, tumor suppressor genes and interferon response pathways. The molecular mechanisms governing tumor dormancy described in this work may provide promising targets for early prevention of cancer and may lead to novel treatments to convert the malignant tumor phenotype into an asymptomatic dormant state.