An RNA editing fingerprint of cancer stem cell reprogramming.
An RNA editing fingerprint of cancer stem cell reprogramming.
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DOI：
10.1186/s12967-014-0370-3
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发表时间：
2015-02-12
影响因子：
7.4
通讯作者：
Jamieson CH
中科院分区：
文献类型：
--
作者：
Crews LA;Jiang Q;Zipeto MA;Lazzari E;Court AC;Ali S;Barrett CL;Frazer KA;Jamieson CH
作用于dsRNA的腺苷脱氨酶（ADAR）对RNA编辑的失调已经涉及多种人类癌症的进展，包括造血系统恶性肿瘤如慢性髓性白血病（CML）。炎症相关的ADAR 1激活发生在白血病干细胞中，特别是在CML的晚期，通常是耐药阶段，称为急变期。然而，在这些罕见的细胞群体中通过RNA测序检测癌症干细胞相关的RNA编辑在技术上具有挑战性，成本高，需要PCR验证。本研究的目的是验证癌症干细胞相关转录物亚组的RNA编辑，并开发定量RNA编辑指纹分析，用于快速检测人类恶性肿瘤中的异常RNA编辑。为了便于使用灵敏的、具有成本效益的方法定量外显子和内含子或3 'UTR灵长类动物特异性Alu序列中的癌症干细胞相关RNA编辑，我们建立了体外RNA编辑模型，并开发了采用位点特异性定量PCR（RESSq-PCR）策略的灵敏的RNA编辑指纹分析。在稳定转导的人白血病细胞系、慢病毒-ADAR 1转导的原代造血干细胞和祖细胞以及原代人慢性髓性白血病干细胞中验证了该测定。在慢病毒ADAR 1表达细胞中，通过RESSq-PCR检测到MDM 2、APOBEC 3D、GLI 1和AZIN 1转录物的RNA编辑增加，其灵敏度高于测序色谱分析。该方法准确检测了原发性慢性髓细胞白血病样本中的癌症干细胞相关RNA编辑，建立了白血病转化的癌症干细胞特异性RNA编辑指纹，将支持临床开发新的诊断工具，以预测和预防癌症进展。RNA编辑定量能够快速检测标志癌症进展和治疗抗性的恶性祖细胞，并将有助于未来的RNA编辑抑制剂开发工作。本文的在线版本（doi：10.1186/s12967-014-0370-3）包含补充材料，可供授权用户使用。
Deregulation of RNA editing by adenosine deaminases acting on dsRNA (ADARs) has been implicated in the progression of diverse human cancers including hematopoietic malignancies such as chronic myeloid leukemia (CML). Inflammation-associated activation of ADAR1 occurs in leukemia stem cells specifically in the advanced, often drug-resistant stage of CML known as blast crisis. However, detection of cancer stem cell-associated RNA editing by RNA sequencing in these rare cell populations can be technically challenging, costly and requires PCR validation. The objectives of this study were to validate RNA editing of a subset of cancer stem cell-associated transcripts, and to develop a quantitative RNA editing fingerprint assay for rapid detection of aberrant RNA editing in human malignancies. To facilitate quantification of cancer stem cell-associated RNA editing in exons and intronic or 3'UTR primate-specific Alu sequences using a sensitive, cost-effective method, we established an in vitro RNA editing model and developed a sensitive RNA editing fingerprint assay that employs a site-specific quantitative PCR (RESSq-PCR) strategy. This assay was validated in a stably-transduced human leukemia cell line, lentiviral-ADAR1 transduced primary hematopoietic stem and progenitor cells, and in primary human chronic myeloid leukemia stem cells. In lentiviral ADAR1-expressing cells, increased RNA editing of MDM2, APOBEC3D, GLI1 and AZIN1 transcripts was detected by RESSq-PCR with improved sensitivity over sequencing chromatogram analysis. This method accurately detected cancer stem cell-associated RNA editing in primary chronic myeloid leukemia samples, establishing a cancer stem cell-specific RNA editing fingerprint of leukemic transformation that will support clinical development of novel diagnostic tools to predict and prevent cancer progression. RNA editing quantification enables rapid detection of malignant progenitors signifying cancer progression and therapeutic resistance, and will aid future RNA editing inhibitor development efforts. The online version of this article (doi:10.1186/s12967-014-0370-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
Greenberger S;Levanon EY;Paz-Yaacov N;Barzilai A;Safran M;Osenberg S;Amariglio N;Rechavi G;Eisenberg E
通讯作者：
Eisenberg E
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
16.6
作者：
Nishikura K
通讯作者：
Nishikura K
影响因子：
24.5
作者：
Chan TH;Lin CH;Qi L;Fei J;Li Y;Yong KJ;Liu M;Song Y;Chow RK;Ng VH;Yuan YF;Tenen DG;Guan XY;Chen L
通讯作者：
Chen L
ADAR1亚型在中国儿童急性白血病中的异常表达。
DOI：
10.1016/j.bbrc.2011.02.025
发表时间：
2011-03-11
影响因子：
3.1
作者：
Ma, Cui-Hua;Chong, Jing-Hui;Zheng, Guo-Guang
通讯作者：
Zheng, Guo-Guang