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基于微阵列和生物信息学的急性髓系白血病长链非编码RNA表达谱分析

Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.

作者信息

Feng Yuandong, Shen Ying, Chen Hongli, Wang Xiaman, Zhang Ru, Peng Yue, Lei Xiaoru, Liu Tian, Liu Jing, Gu Liufang, Wang Fangxia, Yang Yun, Bai Ju, Wang Jianli, Zhao Wanhong, He Aili

机构信息

Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Hematology, The Xi'an Central Hospital, Xi'an, China.

出版信息

Cancer Sci. 2018 Feb;109(2):340-353. doi: 10.1111/cas.13465. Epub 2018 Jan 27.

Abstract

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the expression profile of lncRNAs and mRNAs in AML. Five pairs of AML patients and iron deficiency anemia (IDA) controls were screened by microarray. Through coexpression analysis, differently expressed transcripts were divided into modules, and lncRNAs were functionally annotated. We further analyzed the clinical significance of crucial lncRNAs from modules in public data. Finally, the expression of three lncRNAs, RP11-222K16.2, AC092580.4, and RP11-305O.6, were validated in newly diagnosed AML, AML relapse, and IDA patient groups by quantitative RT-PCR, which may be associated with AML patients' overall survival. Further analysis showed that RP11-222K16.2 might affect the differentiation of natural killer cells, and promote the immunized evasion of AML by regulating Eomesodermin expression. Analysis of this study revealed that dysregulated lncRNAs and mRNAs in AML vs IDA controls could affect the immune system and hematopoietic cell differentiation. The biological functions of those lncRNAs need to be further validated.

摘要

长链非编码RNA(lncRNAs)是长度超过200个核苷酸的转录本,参与肿瘤发生并在癌症进展中起关键作用。为了确定lncRNAs是否参与急性髓系白血病(AML),我们分析了AML中lncRNAs和mRNAs的表达谱。通过微阵列筛选了5对AML患者和缺铁性贫血(IDA)对照。通过共表达分析,将差异表达的转录本分为不同模块,并对lncRNAs进行功能注释。我们进一步在公共数据中分析了来自模块的关键lncRNAs的临床意义。最后,通过定量RT-PCR在新诊断的AML、AML复发和IDA患者组中验证了三种lncRNAs,即RP11-222K16.2、AC092580.4和RP11-305O.6的表达,它们可能与AML患者的总生存期相关。进一步分析表明,RP11-222K16.2可能影响自然杀伤细胞的分化,并通过调节Eomesodermin表达促进AML免疫逃逸。本研究分析表明,AML与IDA对照中lncRNAs和mRNAs的失调可能影响免疫系统和造血细胞分化。这些lncRNAs的生物学功能需要进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d143/5797823/a9c399a5488d/CAS-109-340-g001.jpg

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