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基于竞争性内源 RNA 网络综合分析儿童急性髓系白血病高危潜在生物标志物。

Comprehensive analysis the potential biomarkers for the high-risk of childhood acute myeloid leukemia based on a competing endogenous RNA network.

机构信息

Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, PR China.

Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, PR China.

出版信息

Blood Cells Mol Dis. 2019 Nov;79:102352. doi: 10.1016/j.bcmd.2019.102352. Epub 2019 Aug 2.

Abstract

Acute myeloid leukemia (AML) is a common form of hematological malignancies, the discovery of non-coding RNA (ncRNA) plays an important role in diverse biological processes including hematopoietic differentiation and proliferation. However, the interaction mechanism of key RNAs and their regulatory network in childhood AML are still to be elucidated. RNA profiles were downloaded from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and identified specific lncRNAs, miRNAs, and mRNAs in high-risk group of childhood AML. A lncRNA-mRNA-miRNA ceRNA network in childhood AML was constructed. A total of 2064 mRNAs, 615 lncRNAs, and 60 miRNAs were identified as significantly differentially expressed, and 13 lncRNAs, 7 miRNAs, and 67 mRNAs were incorporated in the ceRNA network. Functional analysis showed that these DEmRNAs were significantly enriched in Ras signaling pathway, TGF-beta signaling pathway, and other tumor-related pathways. Among the network, 10 RNAs (LINC00471, hsa-mir-100, hsa-mir-150, ANP32E, ERMP1, MYO1B, PAPD7, PTGIS, TERF1, and VEGFA) was associated with high-risk group of childhood AML and functions were significant for prognosis. Then, these findings together provide a new insight into the pathogenesis of high-risk group of childhood AML that can assist clinicians clarify the function of lncRNA to guide the treatment and in-depth study.

摘要

急性髓系白血病 (AML) 是一种常见的血液系统恶性肿瘤,非编码 RNA (ncRNA) 的发现对包括造血分化和增殖在内的多种生物过程起着重要作用。然而,关键 RNA 及其在儿童 AML 中的调控网络的相互作用机制仍有待阐明。从 Therapeutically Applicable Research to Generate Effective Treatment (TARGET) 数据库中下载 RNA 谱,鉴定出儿童 AML 高危组中的特异性 lncRNA、miRNA 和 mRNA。构建了儿童 AML 的 lncRNA-mRNA-miRNA ceRNA 网络。共鉴定出 2064 个 mRNAs、615 个 lncRNAs 和 60 个 miRNAs 存在显著差异表达,其中 13 个 lncRNAs、7 个 miRNAs 和 67 个 mRNAs 被纳入 ceRNA 网络。功能分析显示,这些差异表达的 mRNAs 显著富集于 Ras 信号通路、TGF-β信号通路和其他肿瘤相关通路。在该网络中,有 10 个 RNA(LINC00471、hsa-mir-100、hsa-mir-150、ANP32E、ERMP1、MYO1B、PAPD7、PTGIS、TERF1 和 VEGFA)与儿童 AML 高危组相关,其功能对预后有重要意义。这些发现为儿童 AML 高危组的发病机制提供了新的见解,有助于临床医生阐明 lncRNA 的功能,指导治疗和深入研究。

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